Protein Explorer: Versions

Protein Explorer
© 2003 by Eric Martz

Design Features
Known Limitations
Version History
Future Plans

This section is for programmers interested in technical details of the implementation of PE. It touches upon some design features that may not be obvious when using Protein Explorer.

Cookies are Used. The Protein Explorer (PE) uses cookies for convenience. Cookies are not a security hazard and can be disallowed if desired.
Automatic NMR Model Counting. When multiple-model NMR files are loaded, they are detected automatically by querying Chime for the model count. Advanced Explorer then offers an additional option "Select NMR Model" which brings up a special control panel for NMR model selection. This is made possible because my requests to have Chime automatically detect NMR PDB files and behave accordingly, and to add the NMR model count to Chime's 'show info' report, were kindly implemented in Chime 2.0 by Tim Maffett of MDL Information Systems, Inc..
PDB Files via Internet Gzipped. When PDB files are obtained directly from a PDB mirror site via Internet (without first saving the PDB file to the local disk), PE uses a URL at the PDB which transmits the PDB file in gzipped form. This typically reduces transfer time by nearly four-fold. Originally, this was made possible because Jaime Prilusky kindly implemented my request to offer this option from the Brookhaven PDB in 1998. Subsequently, Helge Weissig kindly implemented a similar capability at the RCSB PDB. The trick to taking advantage of Prilusky's enhancement is to use "send-x-pdb" (e.g. www.pdb.bnl.gov/pdb-bin/send-x-pdb?id=9dna) instead of the more usually used "send-pdb" (e.g. www.pdb.bnl.gov/pdb-bin/send-pdb?id=9dna). Also, the former sends the file with MIME type chemical/x-pdb (which can invoke RasMol or Chime) whereas the latter sends the file with MIME type text/html, so it is displayed as text in the browser.
For the RCSB, the URL to fetch a gzipped PDB file for 9dna is: www.rcsb.org/pdb/cgi/export.cgi/9dna.pdb?pdbId=9dna&format=PDB&compression=chime
Javascript Can Query Chime Unambiguously. A mechanism is implemented which, for the first time (12/98), allows javascript unambiguously to query Chime (see shared\cquery.js). It is used, for example, to ascertain whether or not an NMR PDB has been loaded, and if so, to ascertain the model count (see above). The mechanism sends a script to Chime and then parses the result from Chime's message stream. In order to be sure the correct messages are parsed, the script is enclosed between unique marker comments.
Busy Status. PE's javascript now knows when Chime is busy (has not completed a script). The mechanism is that an 'end of script' comment is added as the last line of every script before it is sent to Chime (see top.EOS in shared\s2c2.js and explorer\top_vars.js). Since the messages are now guaranteed to come back in correct order (after unscrambling, see below), javascript knows that Chime is finished when the end-of-script comment comes back. The busy status is used to avoid sending additional scripts to Chime before the execution current script has been completed. In the case of sending 'interrupt' followed by an additional script, failure to wait until each script has completed can result in the intermingling of commands from different scripts in the message stream, a condition the present unscramble() routine is not able to deal with.
Javascript also knows when Netscape is busy, namely, when a document in a frame has not completed loading (busy status is turned on by onUnload and turned off by onLoad). This avoids clicking on links or buttons before all the relevant forms and documents are in place.
The Explorer (one molecule at a time) has a Ready/Busy indicator below Chime. The Comparator does not have such indicators but internally obeys the same rules. This is because the Comparator would need three separate indicators (one for each Chime and one for Netscape) and this seemed not worth the effort for programming nor the screen space required nor the visual distraction from three indicators.
Chime's Messages are Unscrambled. The above capability requires a mechanism to unscramble the order of messages received from Chime (see version 0.95). This was made possible because, at my request, Tim Maffett kindly implemented a mechanism to enable unscrambling. Maffett determined that the scrambling I had reported to MDLI occurs in the plug-in/Netscape interface, and is therefore not under the control of MDLI (and is not a bug in Chime). The mechanism he provided is to add a sequence number to each message sent from Chime to javascript. I was then able to write a javascript unscramble() function (which required over 400 lines of code exclusive of comments!).
To see the unscrambling in action, issue the command "javascript top.db(true)", which turns on a debugging mode. All messages will now be reported to the message window, prefixed by S (for Scrambled) and then U (for Unscrambled).
Temporary disconnect for loops. The unscrambling function requires that out-of-order messages be stored until they can be passed out in order. The NMR [Auto] (automatic display of each model in sequence) uses a looped script which can easily generate thousands of messages. Unlike some non-looped scripts, there is no need in this case for javascript to "scrutinize" the text of each message. Therefore, a special mode was provided in unscramble() for looped scripts -- in this mode, message numbers only are unscrambled, without storing the messages themselves or passing them onto the message text processing function. When every message number is accounted for, and the interrupt has been processed, Chime has completed the script. However even this took too long (javascript being an interpreted language) and after a long period of viewing the [Auto] loop, and after Chime had processed the interrupt which stops the loop, it would take many minutes for unscramble() to process even just the message numbers. During these minutes the user must wait while nothing appears to be happening. (Actually unscramble() is going at top speed but nothing happens on the screen and the user is locked out by the "busy" condition.) Therefore a third mode was implemented, called disconnect mode, to make the [Auto] loop display recover quickly after an interrupt. In disconnect mode, message numbers as well as message texts are simply discarded. After sending the interrupt, a reconnect operation is initiated. In order to determine when Chime is idle/ready, this function checks at one-second intervals and turns off the "busy" flag only after a second in which no messages were sent by Chime. This may not be a bullet-proof method but is the best I've come up with. The worst consequence could be that left-over messages might come back unexpectedly after reconnect signals that Chime is "ready". This would likely generate an illegal condition in unscramble() which would then recommend closing the window (ending the session).
State Maintenance. It is possible to change the documents in any frame without losing the state of the system. This is accomplished by having all state variables (top_vars.js and top_cmpv.js) in the top-level frameset, rather than in any particular document. These variables survive throughout the entire session. It is also convenient to have the shared javascript functions in the top-level frameset. This avoids having references to these functions break when structural changes are made during enhancements.
Management of slow operations.
Surface calculations. Calculation of surfaces and coloring them by distance (QuickViews DISPLAY Surface or Contacts, or in Advanced Explorer, coloring a surface by electrostatic potential, or lipophilicity potential) require significant time. In QuickViews, a small window appears apprising the user of this. For large molecules this may take several minutes, but there is no workaround.
Retaining the selected subset. Several options in QuickViews utilize scripts that involve selecting subsets, but when finished, preserve whatever was selected before the button was pressed. These are the Water, Ligand, and 2^o buttons, and DISPLAY Vines or Cartoon. Restoring the initially selected atoms is accomplished with one final "select temporary", where "temporary" was defined as the initially selected subset. Selecting a defined token is exceptionally slow in RasMol and Chime when the subset is large. After loading a large molecule and pressing the Water button, it is quite possible to have the browser and Chime freeze for a full minute or more. On the other hand, if all atoms are selected prior to these operations, the script can end with "select all" which completes instantaneously. Therefore, PE notices whether all atoms are selected and avoids selecting the defined temporary subset in that case. If a subset of the atoms are selected, and if the "select temporary" operation is estimated to need more than 12 seconds, a warning alert informs the user that selecting all will speed up this operation, but offers the option to proceed slowly, preserving the currently selected set. This implementation required that we estimate the speed of a "select temporary" operation in Chime separately for each client computer.
Determing Chime's speed on each computer. With the help of Diana Ditmore, we first tried estimating the computer's speed with a javascript integer counting loop. Our implementation seriously underestimated differences in computer speeds, and completely failed to predict the speed with which Chime could execute "select temporary" for a test set of 45,000 atoms (1g3i). This remained true when we included random number and square root operations in the loop. We then implemented a method in which a separate window is opened in which a very simple invocation of Chime is used to measure the actual speed of "select temp" in the largest PDB file already contained within the PE file set, 2hhd.pdb. On our reference computer (667 MHz PIII), this usually took 220 milliseconds (though it ranged between 170-330 in replicate tests). We arbitrarily defined this as a relative Chime speed of 1. A 100 MHz 80486 computer had a relative speed 20-fold slower (0.05). A 1.7 gigaherz PC has a relatie speed of 1.7. We suppose maybe the very fastest current computers could have a relative speed of 5, though we have not tested one. Our implementation allows for a maximum speed of 22, allowing for some future increases in speed. PE will show you the relative Chime speed it has determined if you enter the command alias speed. This also gives the option of re-determining the relative speed on the next startup of PE (by erasing the cookie). The document that determines the speed is speed_ch.htm.
The relative speed is determined five times and the average is saved as a cookie with a one-year lifetime. Based on the total atoms in the PDB file, and the number of atoms selected, we predict the seconds needed for the operation requested. (See predicted_sec() in util_top.js.) You can see these predictions if you enter the command speedwatchon before e.g. pressing the Water button. If the prediction exceeds 12 seconds, the user is warned and given the option to cancel, and it is explained that if all atoms are selected first, the operation will be much faster. For test purposes, here are a series of increasingly large PDB files (total atoms in parentheses): 1IGT (13K), 7AHL (23K), 1G3I (45K), 1AON (59K), 1FFK (64K), 1JJ2 (98K). Larger oligomers including huge virus capsids are available from Probable Quaternary Structures (accessed through the Mol Info window).
The first speed detemination is thown away because it often spuriously reports 0 milliseconds (for reasons unknown). Merely reloading the speed-measuring document did not prevent this (if it was the first time Chime was loaded in the Netscape session), so the window containing that document has to be closed and re-opened. Furthermore, on a very slow computer, the second determination may also be 0 milliseconds, so the second determination is thrown away if it is very small. Thus, it takes 6-7 determinations to get five good ones for the average.
With downloaded copies of PE on Macintoshes, version 1.98 Beta of PE revealed that Chime often fails to load into the window containing the speed_ch.htm document, causing PE to fail to start (since no Chime speed is ever reported). Therefore, in PE 1.981 Beta, for downloaded PE on Macintoshes, the speed test is not attempted. Instead, the user is asked whether the computer is a G3 or a G4, and a rough speed is recorded based on the response. Advanced users may determine the speed of Chime on their Mac by running PE on-line and entering the "speed" command. This relative Chime speed value can then be entered in the next session of the downloaded PE for improved accuracy.
Slow color scheme scripts. Several color schemes in PE use Chime scripts (rather than being built into Chime), and are designed to color only the selected subset of atoms. Limiting them to the currently selected atoms involves using the defined "temporary" set in several selection commands, as well as restoring it with "select temporary" as the last command. Because these involve several selections of "temporary", they are even slower than the operations discussed above. PE's predicted seconds for execution takes this into account. If more than 12 seconds, PE reminds that selecting all prior to applying the color scheme will make it much faster.
Because being warned and asking for confirmation for a "slow" operation is distracting and annoying, we tried to err on the side of warning less, rather than more.

Known Limitations

The following limitations remain in version I plan to fix these as time permits.

Chime 2.6 provides "show pdbheader", but Protein Explorer does not yet utilize the newly available PDB file header, e.g. to provide buttons to highlight residues listed in SITE records.
Scripts saved from Chime lack surfaces and other rendering features introduced since RasMol. A script recorder is under development that will solve these problems.
The Sequence and Seq3D displays show nonstandard residues as gaps. An alternative method of querying Chime for sequence information that avoids this problem appears to be possible, but is unlikely to be implemented soon.
Failure of chain color scheme for NMR ensembles. When there are multiple models, the "chain color scheme" built into Chime assigns each model a different color. Since (in non-expert mode) FirstView shows only the first model, multiple chains will all be the same color (blue).
Fixing the following limitations is not worth the time required, so these are expected to remain indefinitely.
MSA3D: Long multiple protein sequence alignments may result in excessively slow listings (over 30 min) and cannot be stopped once started. Alignments over 32K bytes in length won't fit in the form box. A solution was designed and partially implemented when MSA3D was superceded by ConSurf.
Buttons may get confused. When certain states are changed with manually issued commands, or from Chime's menu, related buttons may lose track of the status of the image. For example, if you change the display of the hetero atoms, or toggle spin with the menu, the [Hetero] and [Spin] buttons won't know this. The only consequence is that you may have to push these buttons two or more times to get the desired result.
One Auto-Model at a Time in the Comparator. The [Auto] button on the NMR Model Selection screen toggles automatically through all NMR models, showing one at a time. At present, in the Comparator, there is no mechanism to allow running [Auto] concurrently in both Chimes. This would require additonal javascript code to distinguish the busy status of each Chime and behave accordingly. Currently, there is only one busy status flag (top.chime_busy) which can be set by either of the Comparator's two Chimes or by Netscape with onUnload.

Future Plans
The following new features are planned or in preparation for future releases of PE, but are not yet available for beta testing. We are optimistic that these will become available in future releases since we have received NSF funding through 2004. If one of these features would be especially useful to you, or if you may be interested in collaborating on development of one of these features, or if you have an idea for a feature not listed below, please contact me.

Information in the PDB File Header. At my request, Jean Holt at MDL kindly implemented a new method to access the PDB file header in Chime 2.6, the command "show pdbheader". A mechanism is under development to utilize this so that PE can offer buttons to highlight residues based on information in header records such as SITE, CISPEP, SEQRES, HETNAM, SSBOND, LINK, HYDBND, SLTBRG, and perhaps others.
Prespecification of initial view and description. A mechanism to allow a hyperlink to prespecify not only the molecule(s) to be loaded, but also the initial view(s) to be shown, and the initial descriptions. This will allow an illustration in a textbook to become the first image within PE (same rendering and color scheme), with chapter and page reference and customized initial description. The mechanism will be to include the url to a javascript file (on a web server) as a query parameter in the link to PE. The js file will contain all customized information in a standard format.
Presentations within PE. A template for building presentations within PE. The presentation format will be similar to that for which a template has been offered for several years. By being within PE, the command line and all other PE capabilities will be available to manipulate any image in the presentation.
Open platform for third party enhancements. A mechanism to allow anyone to create a control page (upper right frame) within PE. This would allow information available from a third party database or calculation to be intergrated into PE, providing buttons to highlight the contributed information.
Hydrogen bonds. A mechanism to locate and display all hydrogen bonds, including buttons to show categories such as backbone-backbone, backbone-sidechain, sidechain-sidechain, interchain, water bridges. Preliminary work has been done in collaboration with Mike Sauder, using the HBPLUS package of Janet Thornton with her permission.

Version History

Here's a short version of What's New.

June 1, 2004: Version 2.25 Alpha (Spanish Only).
This update of the Spanish translation of PE was begun in early 2004 with PE 2.1, before PE 2.2 was released. The following improvements (already released in the English versions PE 2.2 and 2.3) were added to the Spanish version. In nearly all important respects, 2.25 is equivalent to 2.3. The major enhancement in version 2.3 that is lacking in 2.25 is the more flexible control of the size of PE's window (from the FrontDoor of PE 2.3).

Enhancements and Changes
On the FrontDoor, when the checkbox "ventana abierta de forma óptima (grande) para nuevas sesiones" is checked, full-screen windows are now opened for PE sessions, regardless of the screen size.
The Features of the Molecule control panel (new in PE 2.1 Alpha) has been presented more clearly, using subtitles and more descriptive labels on some links. Thanks to Frieda Reichsman who suggested most of these changes.
When a session is started, the small yellow window that advises you to wait until the molecule arrives was deemed unnecessary and has been removed. More detailed advice still appears automatically when the molecule takes more than 30 seconds to arrive. Thanks to Frieda Reichsman for suggesting this change.
No longer does a confirmation dialog pop up recommending that you stop spinning. Spinning now stops automatically, without confirmation, after 3 minutes. Indefinite spinning can be enabled with the command alias nss (non stop spin). For details, see spin control. Thanks to Frieda Reichsman for suggesting this change.
Further improvements to documentation, including major revisions of quality of the molecular model, R value, free R, and Ramachandran plots.
All-atom contact analysis (with the MolProbity server) has been added to External Resources. A precis of a recent paper on this new and powerful method for structure validation has been included in Favorite Literature, along with one for another fascinating paper on co-evolution of protein function with fold.
Bugs Fixed
Required Chime 2.6 SP4 for Windows, and 2.6 SP3 for Macintosh. Version 2.6 is the first that supports Features of the Molecule. The SP's fixed serious bugs: see Version History of MDL Chime.
Fixed bugs that caused spurious error messages with some incompatible browsers, such as Safari. Appropriate incompatibility messages are now given in Mac IE, Mac OSX Safari, and on Windows or Mac in Opera, Mozilla, and Netscape 6 or 7. In addition to Win IE 6 and Netscape 4.8, Netscape 4.08 still works on Windows (but not on Mac)! See Browser Compatibility.
Added a new check during startup to verify that PE has permission to open new windows as needed. In prior versions, "pop swatters" caused PE to stall without explanation during startup. This new check is explained in PE's Browser Testing. If PE is blocked from opening new windows, it displays this error message.
When used from a server in Internet Explorer, Features of the Molecule now works if the properly-named and constructed supplementary header data file is provided in the same directory as the PDB file, as explained in Support for Protein Explorer's Features of the Molecule. The easiest way to test this is to click on any of the quick-start molecules at the FrontDoor, while using PE on-line in IE. In 2.1, Features of the Molecule failed to work (and you got an alert in programmer's jargon). Now, Features of the Molecule will be displayed for the quick-start molecules, because the supplementary files are provided.
In FirstView, removed the inappropriate link to "Molecule Information", which was superceded in 2.1 with Features of the Molecule and External Resources in 2.1 accessed from the PE Site Menu.
Features of the Molecule should now work fully on the Macintosh (in Netscape 4.8). In 2.1, only a small portion of the information that was supposed to be displayed in Features of the Molecule was being displayed on the Mac. Thanks to Diana Ditmore for providing this fix.
A bug introduced into PE 2.1 Alpha precluded "Empty" PE (formerly "Bare" PE, see below) from being started with pe.htm in some circumstances. This has been fixed.
Documentation / Terminology
A series of slides entitled Global Protein Structure Issues have been added.
The above mentioned slides and several existing documents have been linked to the FrontDoor under a new section About Protein Structure (as distinct from the existing section "About Protein Explorer").
The following documentation files were updated: this Version History, PE Literature, Troubleshooting, Cookie Requirement, Expert mode, Future Plans, and Help/Index/Glossary. New entries in the latter were added for structural bioinformatics and structural genomics, and some small snapshots of PE were added to clarify locations of PE's parts, e.g. under control panel, message box, entering commands, and selected atom count.

July 7, 2003: Version 2.1 Alpha.

Added Features, a new control panel that makes information in the Header of the PDB file much more accessible. Jean-Philippe Demers, Diana Ditmore, and Rosalia Tungaraza contributed to the implementation of Features.
A new PE Site Map is now linked to all control panels. It replaces the former links to Molecule Information (or Mol Info), Back, Quit, etc. Resources external to PE, formerly in the Molecule Information window, remain in a pop-up window now renamed External Resources. Thanks to Cris Necochea for expert technical advice.
In External Resources (accessed from the new PE Site Map), added a link to Entrez Structure, NCBI. A similar link is also in the pop-up "View All" window for the "Primary Citation" link on the Features control panel.
In QuickViews, added a new DISPLAY Contacts mode: Colored by Chain.
Added new pages Some of my favorite protein structure literature, Protein Structure Bioinformatics Resources, and greatly expanded the page on Literature about PE.
Animations now play smoothly in Windows Internet Explorer (as well as Netscape 4.x). Instructions for saving animations have been improved, especially for use in Internet Explorer. The "failure to start animations automatically" bug mentioned in the previous release was fixed.
A new type of animation has been included in the Atlas: a simulation of a ligand (inhibitor) binding to a protein (HIV protease) with concurrent energy minimization by molecular mechanics. Please see Enzymes in the Atlas.
Links to the Help/Index/Glossary are now green so you can tell where these links will take you. Thanks to Diana Ditmore for this suggestion.
Minor improvements to documentation. The term "control page" has been changed to "control panel" throughout.

What happened to version 2.0? I had planned to make a full release of version 2.0 in 2003, but teaching obligations precluded this. Meanwhile, progress with new capabilities made it unrewarding to spend time on version 2.0, compared to making the new capabilities available.
Sept 15, 2002: Version 1.982 Beta.
Version 1.982 fixed compatibility with Chime 2.6 SP4.

Chime 2.6 SP4 (released September 12, 2002) is now compatible with PE. In IE, PE works in Chime 2.6 SP3 or later; In Netscape, PE works in Chime 2.0.3 or later (see PE-compatible browsers).
Chime 2.6 SP4 has a newly functional "show version" script command, making it much easier to determine its version in IE. However, it was necessary to maintain compatibility with SP3 plus SP4 in IE in order to avoid suddenly locking out instructional computer labs where software changes take a long time to be made (such as the one I teach in at UMass). Because of the difficulties determining versions of Chime 2.6 SP3 and earlier in IE combined with the requirement for a new mechanism for SP4, a major overhaul of the startup mechanism of PE was required. These changes are detailed under Chime Testing.
In addition, there was an unanticipated change needed to support IMBIF, which required additional recoding.
A known bug remains for animations. In IE only, with Chime 2.6 SP4 (but not SP3) animations fail to start animating automatically. Pressing the "Animate" toggle twice starts them. (Fixed in subsequent version.)
The background of the Help/Index/Glossary was changed to light green to make its connection to the green circled question marks on every page more obvious.
Minor improvements to documentation and the Atlas.

Sept 8, 2002: Version 1.981 Beta.
Version 1.981 fixes two serious Mac-specific bugs that have come to light in 1.98.

In QuickViews, control of the coloring of surfaces has been improved. Beginning in 1.98, surface coloring control (with the COLOR menu) was lost when a new DISPLAY menu operation was selected. Now, whenever the Surface Help & Controls message is displayed in the middle help window, the COLOR menu works on the surface instead of the selected atoms. This message can be redisplayed at any time using a link at the top of the middle help frame, until the surface is deleted (DISPLAY *Hide*) or you exit from QuickViews. (In 1.98, deleting the surface failed to stop displaying the Restore Surface Help & Controls link. This bug has been fixed.)
Fixed a bug that prevented Protein Comparator from starting on Macs.
Fixed a bug that prevented downloaded copies of PE from starting on some Macs. PE's startup sequence stalled while testing the speed of Chime (black frame at lower left). This is caused by a thusfar unexplained failure of Chime to load in a child window. This problem did not occur when Macs used PE 1.98 on-line. In version 1.981, with downloaded copies of PE, the user is asked whether the Mac is a G3 or G4, and that information is recorded as a rough speed indicator. Furthermore, on computers where speed testing is attempted, should it stall, the resulting failure to report the speed in a reasonable time (45 sec) forces bypassing of the speed test so PE will start, and a default (slow) speed is recorded. Advanced Mac users may enter a more accurate speed value for a downloaded copy of PE as explained above in Design Features: Management of Slow Operations, and also in the Help/Index/Glossary under slow operations, warnings.
Netscape 4.8 has been released (following 4.79) and works just fine with PE. The browser testing needed no corrections; the documentation has been updated. Instructions for finding 4.8 have also been updated. Version 7 has also been released, but the Chime installer does not yet support it, nor has it been tested with PE.
Added a new entry to the Atlas (3rd item under "Challenging"): DNA mismatch repair protein MutS binding to a mismatch, 1E3M. See if you can find the mismatch in the DNA!
Minor improvements to documentation in several places.

Aug 30, 2002: Version 1.98 Beta.

*** ENHANCEMENTS TO FUNCTION ***
" 2� ", a new convenience button, renders all chains as cartoon and colors them by secondary structure in a single click. It is available on all pages after FirstView.
The new chain coloring scheme Chain (PE) added to QuickViews in the previous release is now the default chain color scheme in FirstView. This color scheme is limited to chains. When there are more, the old "Chain (Chime)" scheme is used. It no longer changes the color of hetero atoms (so in FirstView, they remain colored by element/CPK).
In QuickViews, there is a new option, SELECT Saved. This allows you to save the currently selected set of atoms, and then later re-select the saved set. Thus, when it is time consuming to select an important set, for example, with Seq3D, you can save it to restore later. Each saved set has an associated short description. Multiple sets can be saved; they expire when you quit the session or when a new molecule is loaded (or when you reset the view, in which case you are warned first).
In QuickViews, after using SELECT Clicked, you can now re-select the click-selected atom set anytime until you load a new molecule or quit the session. The re-select option appears in the middle frame after SELECT Clicked.
In QuickViews, there is a new option to SELECT Neighbors (within a specified distance of the previously selected atoms).
In QuickViews DISPLAY Contacts there is a new checkbox, before the contact surface display is constructed, to hide contacting water.
In QuickViews, DISPLAY Dots now offers radio buttons to control dot density.
In QuickViews, *Hide* has been reorganized to make more sense, and now subsumes the old Hide Selected. There are now checkboxes to hide each category of display, and an new option Hide everything.
In QuickViews, it is now possible to apply a uniform color from the COLOR menu to a Surface.
Two new options on the QuickViews DISPLAY menu are Sequences and Evolution. The latter provides a connection to ConSurf. These two options also remain available in the Mol Info window.
In Comparator, the inactive molecule is now indicated with a gray background. There is a new Preference that disables this behavior.
No longer will a huge molecule paralyze your computer for minutes without warning, at least for some of the most common operations. Some slow operations are now faster, and you are warned when they will be slow, and reminded that preceding them with SELECT All will make them much faster. The operations affected are the buttons for Water, Ligand, and 2�, DISPLAY Vines or Cartoon, and COLOR Polarity2/3/5 or ACGTU/bb. This involved determining the speed of Chime on your computer! See Design features for details. Thanks to Diana Ditmore for help with this project.
The ability to set the best server to provide PDB files has long been a preference, but has only now been added at the bottom of the newer Preferences page (accessed with the link below the message box). Previously, it was accessed with the circled blue question mark near the PDB ID code slot on the Load Molecule page.
Many bugs were fixed, including

In QuickViews, the SELECT menu was corrupted when changing between top and bottom in Comparator
In QuickViews, DISPLAY Cation-Pi or Salt Br. did not work with NMR ensembles.
When PE opens its optimal (large) window (checkbox on FrontDoor checked), it no longer hides the Windows taskbar.
A bug introduced in 1.922 that slowed down the display of FirstView.

Scores of small enhancements not listed here were implemented.
*** ENHANCEMENTS TO DOCUMENTATION ***
A new What's New was written summarizing the differences between PE 1 and 2.
The 1-Hour Tour (formerly called the QuickTour) was revised to use some of the new features.
Many of the QuickViews help documents (displayed in the middle frame) were revised, and some new ones were added. See especially SELECT Solvent, Water, Cystine, and DISPLAY HBonds, SSBonds.
New instructions are provided for Making an Animated GIF File with Protein Explorer. The method is based on an enhancement in the NMR Models/Animation control page. The automatically-generated animation script now runs in both Chime and RasMol and, when run in RasMol, can be used to save the GIF file frames needed for assembling an animated GIF.
Lesson Plans were revised to include a wonderful integrated set of biochemistry exercises by Feig and Jabri.
The disadvantages of using PE in IE, as compared to Netscape, have been listed in a new document How and Why does Protein Explorer (PE) work better in Netscape 4.7X than in Internet Explorer (IE)?
Hyperlinks that start PE and pre-specify a molecule to display can be dragged and dropped into Netscape Composer to create selections of molecule-specific links. A new document on Dragging and Dropping Existing Links tells how.
The document on compatible browsers has been revised and improved. IE 6 was tested and found compatible.
The effects of enabling the Expert Mode preference have been documented.
Numerous entries have been added, expanded, or revised in the Help/Index/Glossary.
Installation of downloaded PE has been improved. There is only a single file to download, and instructions for starting PE have been improved. The new procedure eliminates the danger of inadvertantly unzipping zillions of files on the Windows Desktop, and facilitates the incorporation of additional subdirectories in future releases.
The Atlas of Macromolecules has been further expanded.
Troubleshooting was revised and now includes the procedure for fixing Windows systems where IE cannot process scripts sent to Chime because of idiosyncracies in Windows plugin management.
Provided a partial list of publications that cite PE.
A visitor meter was added to the on-line FrontDoor between versions 1.901 and this version. Since the majority of those visitors don't ever run PE, I've added a second meter as a pop-under window invoked by QuickViews. See Visitors. And there is a third meter at the bottom of the Atlas of Macromolecules.
I decided not to spend the time to enable Tutorial movies (example) to run in IE. If you try, the situation is explained. There are only 3 movies in the Tutorial, the Tutorial is partially obsolete, and the movies still run in Netscape.

February 24, 2002: Version 1.922 Alpha.

The Atlas of Macromolecules has been greatly expanded, and illustrated.
A new "chains" color scheme has been added in QuickViews, Chains (PE). The chains color scheme built into Chime has been renamed Chains (Chime). The colors in the new scheme are more easily distinguishable, but are limited to 12 or fewer chains.
The number of chains is now reported in the Molecule Information Window. Discussion of chains has been revised and expanded in the backbones link at FirstView and in the Help/Index/Glossary.

February 21, 2002: Version 1.92 Alpha.

An Atlas of Macromolecules has been provided. It is linked to the FrontDoor under More Quick-Start Molecules, and to Lesson Plans.
Seq3D has a new checkbox "All identical chains". When checked, clicking on a residue, or range of residues, in the first of a set of sequence-identical chains highlights and selects that residue in the entire set of sequence-identical chains.
Seq3D has a new option "no change" for the display rendering of clicked residues, and new colors including "unchanged". Wording has been clarified, and range-reporting slot has been moved to the middle frame, next to the touch-to-identify reporting slot, so both are always in view regardless of scrolling in the bottom sequence-listing frame.
The Sequences page now states the total number of chains at the top, and has a new summary line that indicates any sets of sequence-identical chains.
The Troubleshooting guide has been extensively revised to include IE and the new 1GIG MacG4 memory problem.
Bug fixed: In PE 1.91, many options in QuickViews' DISPLAY and COLOR menus failed to operate in Netscape, only when PE was downloaded. (They did operate in IE, or in Netscape on-line.)

December 20, 2001: Version 1.91 Alpha.

The major enhancement in this version is the ability to work in Microsoft Internet Explorer in addition to Netscape. Achieving this required that a large number of IE/Chime-specific bugs and idiosyncracies be discovered, understood, and worked around. For those interested, technical details have been documented for browser and chime version testing and for implementation of PE in IE. The miracle is that it was possible, and the performance in IE is smooth and reliable! I am very grateful to Paul Pillot and Jean-Philippe Demers, each of whom made crucial contributions to PE's ability to work in IE, and to MDL for quickly adapting Chime to Microsoft's sudden change in IE5.5SP2.

IE 5.5 SP2 is the earliest version that is supported, and for this, Chime 2.6 SP3 is required. Netscape 4.08 and later versions remain compatible, and will work with Chime 2.0.3/2.0a or later. Browser and Chime version checking were redesigned and improved as described in the new document browser and chime version testing.
PE's control over the size of the window it opens for each new session has been redesigned and adapted to the complexities of two browsers. By default, a checkbox (state maintained by a cookie) is checked on the FrontDoor, "Open optimal (large) windows for new sessions". If the user leaves this checked, and if the screen resolution is adequate, PE will open directly (without an intervening screen-size message) in both browsers. A summary of the design is in Implementation of PE in IE. The explanation for the user is in the new document Window Size Control in PE.
A new server, ConSurf, has superceded PE's MSA3D. It is now linked in the Molecule Information Window. For more information, see Visualizing Regions of Conservation in 3D Protein Structures (normally accessed by clicking on "Color by multiple sequence alignment" at the upper left corner of the FrontDoor.)
A new document, publications about PE, has been provided.
MSA3D had a bug affecting PDB files with multiple protein chains. If no chains are specified in the chains-slot on the MSA3D form, the first chain is checked for sequence identity with the aligned 3D sequence, but all chains are colored. If the protein is a hetero-oligomer, colors in the sequence-nonidentical chains were meaningless. A warning message has been added requesting that the user specify chains for multiple-chain PDB files.
The MSA3D Guide (formerly called the MSA3D Tutorial) has been improved in content and organization. New sections address Characteristics of alignments suitable for MSA3D, Ready-made alignments from HOMSTRAD, and Visualizing the Sickle Hemoglobin Mutation in MSA3D.
The Mol Info button has been changed to a link to improve consistency -- buttons change the molecular graphic, while links don't.
When the "expert" preference is set, PE automatically goes from FirstView to QuickViews (instead of Advanced Explorer). If an NMR ensemble is loaded, it goes automatically to NMR Models/Animation.
A new method of running PE in x86 linux has been mentioned.
Other clarifications were made and minor bugs fixed.

August 31, 2001: Version 1.901 Beta.

A bug was fixed that caused MSA3D to color the wrong residues in the 3D structure. The problem occurred only with chains in PDB files where the first residue is assigned a sequence number less than one. The result was that the colors on the 3D structure did not agree with the colors in the alignment listing. Examples are 1AVQ (starts with -1) and 1BXW (starts with 0). Thanks to Hannah Wexler of UCLA for discovering this bug and reporting it. This bug had been present since MSA3D was first released over a year ago.
In MSA3D, running any of the first 3 of the 4 ready-made examples popped up warnings "Chime script ... unrecognised command!". This bug, which caused no errors in the alignment listing or molecule coloring, has been fixed.

August 25, 2001: Version 1.90 Beta.

The copyright statement (FrontDoor) has been clarified explicitly to permit free local distribution of PE to students in classes within an educational institution.
A list of FAQ has been added.
The Assessment page has been enhanced to offer on-line assessment of your entire course, or just the Protein Explorer portion, with a free, customizable website.
In QuickViews, DISPLAY Contacts, Step by step, a number of bugs were fixed, some items were clarified, and improvements were made in the ability to repeat this process at arbitrary points. Also, the "Zoom+" and other buttons (except Center) no longer remove the step-by-step checkbox sequence from the middle frame, allowing these operations to be done during the process of building the contact surface image.
In QuickViews, DISPLAY Surface, the help was clarified, and controls were added to the help frame to hide the surface or make it transparent. Also, a link was provided to enable easy return to the Surfaces help/controls after other operations have been performed.
On the Animations page (accessed by clicking on the animated EF hand image at the upper left of the FrontDoor), a new morph has been added for lipase (thanks to Byron Rubin).
Detailed instructions for mutating a PDB file with DeepView were provided (linked to the Help/Index/Glossary).
Instructions for constructing a PDB file showing crystal contacts with DeepView have been greatly improved. These are normally accessed from the Molecule Information Window, from a link in the document on Crystal Contacts.
The red and yellow icon for the Molecule Information Button has been retired in favor of a button labeled simply "Mol Info".
On Seq3D, a new color option, "Green", has been added to the menu of colors for display of clicked residues.

August 5, 2001: Version 1.89 Beta.

A first stab at a list of lesson plans on macromolecular visualization has been provided. It will grow -- please contribute!
To accompany the lesson plans, a form has been provided for Student Assessment of Learning Gains from Protein Explorer.
In MSA3D, generation of the Alignment Listing window has been speeded up considerably (see the checkbox at the very bottom of the Alignment Form). Also, a new and very pretty ready-made example has been added for a translation repressor PUF, that binds to the 3' untranslated region of mRNA (thanks to David S Bernstein, U Wisconsin, Madison). The Alignment Form contains new information about alignments too long to fit in the box, and RNA alignments.
In Advanced Explorer, and in the Glossary, Documentation is provided for a better method of rendering surfaces colored by MEP.
Project folders are a feature for advanced users. Several versions ago, a bug was introduced that prevented setting project folders. This has been fixed. Additional code has been added to ensure that PE handles gracefully two error conditions that can arise regarding a previously set project folder: the absence of the file pe_proj.htm, or an obsolete version of the file pe_proj.htm. Thanks to Frieda Reichsman for pointing out the bug.

July 15, 2001: Version 1.88 Beta.

In QuickViews, DISPLAY Contacts, there is a new option to build the contact surface display step by step. This makes it easier for beginners to understand the contact surface display, and provides more control over the final image by making it possible to stop at any step.

July 3, 2001: Version 1.87 Beta.

An introduction to homology modeling has been provided. It can be accessed through the help/index/glossary.
The help/index/glossary has been increased to over 150 terms. It can now be accessed by clicking on any control page within PE.
The 1-Hour Tour has been revised and expanded. A more prominent link to it is on the FrontDoor. A section had been added called Beyond the 1-Hour Tour.
In QuickViews, DISPLAY Contacts now shows a progressive series of images designed to help novices understand the contact surfaces display more easily. This series is not shown when the Expert Preference is set, nor when an NMR ensemble is loaded. In these cases, the final image is shown all at once.
In the QuickViews help for the Polarity5 color scheme, a link has been added to a server that calculates the pI.
Changes were made in preparation for a future release that will support Presentations in Protein Explorer.

April 24, 2001: Version 1.86 Beta.

A new glossary, index, and help document has been begun. It is accessed by clicking the green circled question mark at the title of any control page , or from the Molecule Information Window. It will take a few more releases until this is reasonably complete.
Information available in the Molecule Information Window has been enhanced, and now includes

An introduction to the EBI Probable Quaternary Structures site, with examples and a link to the PQS page for the current molecule.
An introduction to crystal contacts, with examples, snapshots, a Chime presentation on the case of malate dehydrogenase (where crystal contacts appear to affect conformation), and a method for generating a PDB file for visualizing crystal contacts using DeepView and RasMol.
Methods for obtaining fewer or single chains from PQS, ExPASy's ExPDB, or with RasMol.
A link to the KUN/WHATIF PDB Report for the current molecule, giving information on the model quality.

Thanks to Steve Johnston (Whitehead Inst.) for pointing out that the molecule information icon didn't look like a button. It does now.
QuickViews Plus (at the bottom of the QuickViews menu page) has a new checkbox to include all models in the contact surface rendering. This supports the display of crystal contacts, using PDB files having the asymmetric unit in model 1, and the crystal contacts in model 2.
The DISPLAY menu of QuickViews has a new option: Vine.
The Contact Surfaces controls (in the middle help frame) in QuickViews have a new option, to display the surface as dots. This is especially useful for small ligands and drugs.
The Contact Surfaces display of QuickViews has been enhanced to show single non-bonded atoms as small spheres. For example, a water molecule near the surface may produce proximity coloring, but be non-bonded (not a large ball) if there are no possible hydrogen bonding donors or acceptors beneath the surface at that position. Formerly, such a water molecule was not rendered at all.
Some typographical errors in the salt bridge report (linked to the help frame in QuickViews) were corrected.

March 16, 2001: Version 1.85 Beta.

Animation of ensembles of models has been greatly enhanced. Access is via Advanced Explorer, under NMR Models/Animation. The button formerly labeled [Auto] is now labeled [Animation].

Faster than before, without crashing (previous versions crashed often). Speed limited only by size of the PDB file.
Several displays and color schemes can now be selected for animations.
The animation can be saved as an html file and played back later in Netscape, without running Protein Explorer. A title can be specified.
Animations can be zoomed, centered, have stereo toggled, or have background toggled while running.
Delays at the ends of animations are now optional (Ends checkbox).
Custom animation scripts may now be divided into an initialization block (run only once, specifying the color scheme and center) and a loop block (displaying each frame). This improves speed and allows initialization of orientation, centering and zooming, yet permits orientation, center or zoom to be changed while the animation is running.
Animation scripts are displayable, for copying and use in constructing presentations.
A single PE session can open multiple animations concurrently.
Different PE sessions can open animations concurrently.

An introduction to animation, with several examples of morphs (some new) and ensembles simulating thermal motion, is accessed by clicking on the animated GIF on the FrontDoor, or from the help buttons (blue question marks, circled) on the NMR Models/Animation page.
A slot was provided on the FrontDoor page for pasting a URL to a PDB file on a server. Pressing [Go] then starts PE to load this PDB file from the server. Examples are provided to try out.

March 11, 2001: Version 1.81 Beta.

A new 1-Hour Tour guide has been added. At this point, only the first of several sections has been completed. This is designed to enable a beginner to learn how to visualize the fundamental structural features of a protein in about an hour.
The order of items on the QuickViews DISPLAY menu has been revised. "Center" was removed since it is superceded with the [Center] button.
An additional option for the QuickViews Contacts display (in the help panel) displays atoms "inside + outside" the surface. This shows covalent bonds (if any) between the two groups.
QuickViews: After SELECT, Nucleic, the "distinguish DNA from RNA" routine has been enhanced to show the counts of pentose C2' and ribose O2' (in the message box). These counts make it easy to check whether every C2' has or lacks an O2'. Also, it now leaves "nucleic" selected upon completion.
The QuickViews help for the [Ligand] button now mentions how to look up the full name for a 3-letter ligand abbreviation in the PDB header.
The QuickViews help for HBonds now includes a figure with information about typical lengths of hydrogen bonds.
A new guide to troubleshooting Chime and PE has been provided.

December 29, 2000: Version 1.80 Beta.

A new option has been added to the QuickViews menus: SELECT Clicked. Atoms, residues, or chains can be selected with mouse clicks.
In the QuickViews Contacts display, the Contacts help frame includes new links to many options: make the surface transparent, hide it, restore it; hide the non-contact portions of the surface; show or hide the atoms bonded to, or 7 Å from, either side of the surface. There are also convenience links to change the color of water, and show thin backbone traces. All these links select the corresponding atoms, for use in subsequent DISPLAY or COLOR menu operations.
In the QuickViews Plus Options, changing the diameters of DISPLAY modes now automatically updates the image.
Fixed (we think) the dreadful bug that reported Fatal error -- this is not your fault. This problem occurred only during startup of PE (not during a session after successful startup) and only on rare computers (mostly fast Win2000 or WinNT systems), but on those it sometimes happened in most startups. None of the computers used for development (including one fast Win2000 system purchased with the intent of debugging this) showed the bug often enough to debug it. Thanks to Tim Driscoll for trapping information that enabled this to be fixed.

November 14, 2000: Version 1.72 Beta.

Spin control. People were observed letting one or more spinning sessions go into the background, resulting in their computer performance being severely degraded -- "freezing". A new warning cascade has been implemented to urge people to stop spinning when they don't need it. Nevertheless, if you want a demonstration to spin permanently, this is easily achieved by canceling both warnings.
Shared folder verification. During startup, PE now verifies that the shared folder exists, and that the files therein are of the same version as PE itself. If not, it explains what to do.
Colored with DRuMS icon button links were added where appropriate.
The small black window offering more information about MSA3D in Netwatch, Science Sept. 1 2000, no longer pops up every time the FrontDoor is loaded.

October 4, 2000: Version 1.71 Beta.

Fixed a bug that prevented PDB ID codes from being loaded (Ouch!). The bug incorrectly reported that Chime 2.0.3 was not installed when in fact it had been. Also fixed another bug that caused the PDB ID code slots on the FrontDoor page to fail to work (Ouch!). These bugs were first introduced in version 1.7.
Offered, to teachers, answers to the tutorial study questions (see link at top of study question page; study questions are accessed from the tutorial, which is accessed from the link on the FrontDoor page, under About PE).
For Macintoshes, improved sizing of the message window vs. frame size.

October 1, 2000: Version 1.7 Beta.

Revision of the Tutorial has been completed, and more Tutorial Study Questions were added.
Quickviews Plus Options have been added to the bottom of the QuickViews page. These change the logic between consecutive SELECT and DISPLAY operations, and allow control of the thicknesses of backbones, traces, sticks, and the radii of spacefilled spheres.
More predefined protein terms are included in the SELECT menu (which has been reorganized), and the help for such selections offers Kurt Gile's Venn diagrams of these terms.
More plain colors were added to the QuickViews COLOR menu.
Access via proteinexplorer.org was established.
The zoom alias z has been changed to Z because the lower case alias interferes with the command rotate z {angle}.
Many miscellaneous minor bugs were fixed, and minor improvements made.

September 7, 2000: Version 1.485 Beta.

The first half of the Tutorial has been revised to reflect the major changes in this version. Work to complete the revision continues at high priority (since I'm teaching a class from it that began, coincidentally, Sept. 7, 2000). The tutorial is currently linked to the main entry page (index.htm), and to the About PE page accessible from the copyright notice on all pages. More explicit links to the tutorial will be reinstated in a future version.
Tutoral Study Questions have been provided in a separate document.
The Advanced Level Form for Recording Observations has been expanded.
The document listing why PE is easier to use and more powerful than RasMol was revised.
A Center button has been added to the convenience button bar accessible from all pages. Thanks to Tim Driscoll for this suggestion. (To conserve space, the Seq3D link was deleted from the button bar. Seq3D can be accessed from the Molecule Information Window.)
New QuickViews DISPLAY options are HBonds and SSBonds.
New QuickViews SELECT options are Helices, Sheets, Hydrogen, Inverse, and Clicks. The latter allows form-based control of measurement of distances, angles, dihedral angles, display of monitor lines (with or without distances), and labeling atoms with custom labels and fontsize.
A new adjunct to the QuickViews SELECT menu is a menu of boolean operators (And, Or, Not) to relate the forthcoming selection to the previous one. This will probably be moved to the bottom of the QuickViews page in a future version to unclutter the top, as additional options are likely to be added (e.g. adding a display mode to the existing display of the selected atoms, rather than replacing the old display mode with the new).
The "Unable to allocate shade" and resulting miscoloring now produce an alert, directing the user to COLOR >Help<, where a fix is explained.
A (Repeat) option has been added to the QuickViews SELECT, DISPLAY, and COLOR menus. It re-executes the previous selection. Thanks to Tim Driscoll for this suggestion.
Seq3D can now accumulate selections, allowing any arbitrary set of residues or ranges to be selected easily.
Netscape 4.08 is the earliest version now compatible with PE. Earlier versions of PE allowed 4.04. Netscape Communicator 4.75 is recommended. (Communicator 6 remains incompatible with Chime!)
Miscellaneous minor bugs were fixed, and minor improvements to documentation were made.

August 10, 2000: Version 1.481 Beta.

The project folder is now set with a browse button. This avoids mistyping the path and other problems. (See the link "Project Folder" below the message box.)
Miscellaneous minor bugs were fixed.

August 1, 2000: Version 1.48 Beta.

Cation-Pi interactions and Salt Bridges can now be displayed automatically, either from QuickViews' DISPLAY menu, or from Advanced Explorer's new Cation-Pi/Salt Bridge branch. A tutorial is provided, which includes a gallery of snapshots.
MSA3D has been improved, tested much more thoroughly and further debugged. It now has an option to display the sequence alignment in black and white (for printing). Sliding adjustments can now be specified at multiple points. A tutorial has been provided.
QuickViews SELECT menu has a new option: Element.
When changing between the top and bottom molecule in Comparator, the QuickViews frame no longer has to reload in order to update the list of chains on the SELECT menu. Thanks to Tim Driscoll for telling me how to do this!
Numerous other bug fixes and small improvements were made.

June 16, 2000: Version 1.47 Beta. Special thanks to Paul Stothard whose permission to use his alignment scripting and coloring code greatly accelerated development of the MSA3D enhancement.

MSA3D. Molecules can now be colored according to conservation/mutation frequency based on an externally prepared multiple protein sequence alignment. MSA3D is a feature of Advanced Explorer.
Seq3D. The rendering controls in the top frame of Seq3D have been simplified.

June 3, 2000: Version 1.46 Beta. Special thanks to Frieda Reichsman and Tim Driscoll who suggested many of the improvements in this version.

New Entry Pathway. The lead-in pages have been further streamlined. One page has replaced three. Starting at index.htm, it takes only two clicks to enter Protein Explorer.
Session Name. Each PE session (window) is given a name automatically, which includes the PDB ID code if prespecified. The session name can be edited before entering PE, and appears at the top edge of the Netscape window. If several sessions are open concurrently, the session name assists in selecting the desired window to bring to the foreground.
Troubleshooting for PDB file network transfer. When PDB files are requested through the Internet, if they don't arrive within 30 sec, a troubleshooting window opens automatically. This explains how to change the PDB mirror URL being used, and how to cancel the session cleanly without waiting for the molecule to arrive.
The FirstView page was put into more logical order.
The Record of observations form was split into two forms, basic and advanced level, and provided also as PDF for easier printing.
Nucleotide Sequence Colors Fixed. Previously, in the sequence or Seq3D listings, nucleotides were colored as though they were amino acids. Now the DRuMS color scheme for nucleotides is used by default, and checkboxes are available to disable coloring for selected nucleotides.
Redundant chain names bug fixed. Frieda Reichsman brought to my attention some PDB files which have several chains with the same chain name. An example is 1acb which has three chains named "E", cleaved from a proenzyme chain. PE's Sequence and Seq3D interfaces now work properly with such files.
Comparator Windows reset bug fixed. In Windows Comparator, a reset initiated with the bottom molecule selected loaded the top molecule into both positions. This is fixed.
A new color scheme, polarity2 was added (in addition to polarity3 and polarity5).
Self-closing of accessory windows. Most accessory windows which can be opened in PE now close themselves automatically when the top level session window is closed. The Molecule Information window still does not automatically close (bug to be fixed in future).
Invisible molecule bug fixed. A bug was fixed that made the FirstView invisible for a certain variant of PDB file format for micromolecules (coming from the Woodcock site at Okanagan U).
Miscellanous. A number of small enhancements were made, including enhanced scope of the expert mode selectable under Preferences.

May 22, 2000: Version 1.45 Beta.

New Entry Pathway. The lead-in two pages have been redesigned. The second page now contains examples of several ways in which PE may be entered, most prespecifying the molecule(s) to be loaded. More importantly, the sequence of information and controls during entry have been redesigned. It is now anticipated that in most cases the molecule(s) will be prespecified by a hyperlink to PE. If no molecule is prespecified, PE immediately offers the Load Molecule page.
FirstView Description. The first page seen after loading a new molecule now contains extensive documentation about the intial view, including explanations of backbone rendering; water, hetero atoms and CPK colors, and disulfide bonds. This leads into the next page, the "QuickViews" control page.
QuickViews. An entirely new interface for manipulating the view has been provided called "QuickViews". It is designed to make it as easy as possible for novices to use simple select/render/color/center operations to manipulate the view, without knowing any Chime/RasMol command language or the terminology for predefined atom sets. It includes extensive explanations and help which appear automatically in a new (4th) frame. Over 5,000 words of help have been added for the QuickViews interface.
Molecule Information Button. A new molecule-information button icon appears on all pages as part of the convenience button cluster. It pops up a window which displays the brief description of the molecule (from the PDB HEADER and COMPND records), shows its PDB ID code, and provides links to display the PDB file header, the RCSB Structure Explorer page for this entry, and the amino acid/nucleotide sequence.
Sequence. A new display of the loaded molecule's one-letter amino acid or nucleotide sequence has been provided. Individual amino acids or groups with similar properties can be optionally color highlighted in the sequence listing. Touching a residue with the mouse displays its chain, 3-letter code, full name, and one-letter code mnemonic. Examples are listed illustrating a range of sequence irregularities, including gaps and insertions, and how to interpret them. The Sequence display is a wide display which covers the molecule, since it does not interact with 3D structure. In contrast, a more abbreviated display, Seq3D, leaves the molecule visible for interaction.
Seq3D. A new interactive sequence-to-3D interface has been provided. The sequence of the loaded molecule is displayed in one-letter code. Clicking on a residue or range of residues changes the rendering and color scheme according to user-selectable options. A [Seq3D] button is included in the button group on every page.
Startup vs. New Window. Startup has been redesigned. All startup is now via the single entry point pe.htm, which automatically opens a new window only when needed. If the hyperlink to pe.htm designates a target window which does not exist (thereby opening a new window for PE), PE detects and uses this window (history.length == 1, top.history.length == 1, top.frames.length == 0). If not, PE detects that it is in an old window or frame, and automatically opens a new window for itself. PE's Quit button always closes the top window containing PE.
Concurrent Sessions. When the link to pe.htm does not open a target window, pe.htm automatically opens a new window for PE. In this case, each window is given a new name. This allows multiple PE windows to be open concurrently. Each PE session is titled with the PDB id code or filename if prespecified, making it easy to find the desired session when several are running concurrently. See Construction of Hyperlinks to Protein Explorer. Now the Noncovalent Bond Finder can be operated concurrently with Protein Explorer.
The option to Resize the window before PE starts has been redesigned. It now works on Macintoshes as well as Windows. New query parameters allow links to bypass the default option to resize the window, and (if a single molecule is prespecified) to bypass the default option to specify a second molecule, thereby invoking the Comparator. The documents about starting PE from hyperlinks have been reorganized and revised, and are summarized in Constructing Hyperlinks to PE.
Button bar enhancements in the group of convenience buttons on every page. A new Reset button reloads the molecule, restoring PE's initial view. a Slab toggle button has been added. The Seq3D button (see above) is available on every page. The Synch button's action now toggles bidirectional following (available on Windows only due to bugs in Macintosh Chime and Netscape).
Changes in Button names/functions. The "Hetero" toggle button has been renamed to Ligand. The intermediate "dots" rendering of the Water button has been removed. The Water button now toggles simply between spacefill and invisible. Also the Water and Ligand buttons have been changed so that they preserves the previously selected atoms, rather than leaving water or ligand selected. The Bkg button now toggles simply between black and white (the intermediate gray background mode has been removed).
The Load Molecule page has been redesigned to offer its options more clearly, in a more logical order.
Expert mode. A new preference setting has been added for experts. When checked, some help intended for novices is not displayed. After a molecule is loaded, the "FirstView Description" page is automatically changed to the "Explore!" page, skipping the "QuickViews" page (which remains accessible from the "Explore!" page). In nonexpert mode, after 10 commands have been entered manually, the user is notified about the existence of expert mode.
Bidirectional NMR movies. A new checkbox was added to the NMR Model Selection control panel. It enables the series of models to play as a bidirectional movie. Previously, the movie could be played only forward.
Better error handling. I have tried to handle these conditions gracefully; that is, with an explanation and without a hang or a crash.

Invalid PDB ID codes. (Must be 4 characters beginning with a digit in the range 1-9). Examples: aaaa, aaaa + 1aa, 1d66 + d166.
PDB files with no sequence (no residues designated as amino acids or nucleotides). Example: 1tn1 or any micromolecule such as ATP.
"Chains" containing a single residue. (Their alpha carbons or phosphorus atoms are displayed as a ball to prevent them from being invisible in the initial backbone rendering.) Example: His tag, chain B in 1b07.

New command aliases have been added in each new version, but were not listed below. You can always see the complete list by clicking on the "Aliases" link under the message box.
Netscape Communicator 6 has been disallowed because it is currently incompatible with Chime 2.0.3.
Over a hundred other minor improvements and bug fixes were accomplished.

September 20, 1999: Version 1.0.

It took a year of work to achieve this version 1.0, yet it is far from finished. I have many plans for the Protein Explorer and will continue to develop it as fast as I am able. At present, it comprises over 10,000 lines of HTML, over 5,000 lines of javascript, and over 500 lines of RasMol/Chime script.
At long last, a first draft of the tutorial is finished. I did not feel it appropriate to assign the version number 1.0 to PE until it had a tutorial. The tutorial now contains links which run "movies" in the PE. A nice one is the first one under Hydrogen Bonds (27.A.ix). (You have to open the tutorial from within the Explorer in order for the movie link to work -- just click on the green question mark and go to Tutorial section 27.A.ix.)
A new control panel, Color Schemes, has been added, containing the two schemes which I considered most needed. Other schemes will be added in future releases.
A slot showing the count of atoms selected has been added below the molecular graphic in the Explorer (but not in the Comparator).
Disulfide bonds are now shown in the initial view immediately following loading, and the number of bridges is messaged. (With NMR files, an incorrect number of bridges is reported because inter-sulfur distances are scanned without regard to models -- a bug in RasMol/Chime.) SS bonds are also shown in the default view on the NMR Model Selection panel (one model at a time, correctly).
One-residue 'chains' are no longer invisible in the initial view. Alpha carbons and phosphorus atoms in nucleotides are now spacefilled in the initial view at a radius identical to the backbone radius. Thus they are invisible within the backbone of multi-residue chains. This was done so that one-residue chains are not invisible in the initial view -- they are now shown as tiny spheres (one must look carefully to see them!). There are over 90 PDB files containing one-residue 'chains' which are invisible if all 'chains' are rendered only as backbone. An example is 2csm.
Long load URL's. Chime 2.0.3 fixed a bug which prevented use of URL's longer than 70 characters in load commands in Windows. PE now allows long load URL's unless a version of Chime prior to 2.0.3 is installed. This problem affected mostly Windows (the limit on Macs is large enough not to cause many problems).
RCSB PDB. The above bug fix newly allows Chime to load PDB files from the RCSB servers. These have now been added to the "Record Preferred PDB Mirror" dialog.
A page demonstrating hyperlinks which pre-specify molecules from diverse third-party servers has been provided.
Resizing the window containing PE, or dragging the frame boundaries, is now better handled (with an onResize in shared/cmd2way2.js).
Further improvements have been made in fitting the command slot and message box optimally into various window sizes, and in the size of the molecular graphics frame relative to the control frames. Whether or not the command slot buttons appear next to it, or out of the way at the bottom, is a new preference.
As a convenience, focus is automatically returned to the command slot upon completion of many operations (any ready condition, all mouse clicks to identify atoms, the completion of any script).
http URL's allowed in script and load commands. "script" and "load" commands which use an "http://"-containing URL are now allowed even when a local disk project folder is not set. Note that load or script commands within the primary script must also use absolute URL's even for files in the same folder on the server. As a simple example of such a script, load and spacefill any protein, then paste this into your command slot and press enter:
script "http://www.umass.edu/microbio/chime/shared/cs_amphi.spt"

PE @ EBI. This version is compatible with the EBI Protein Quaternary Structure server, where (thanks to Kim Henrick) it is now offered as a viewer. For example, 2hhd.pdb contains only half of the hemoglobin tetramer; to view the entire tetramer in PE, go to pqs.ebi.ac.uk/pqs-bin/macmol.pl?filename=2hhd.
Help buttons have a new look.
PDB's via ftp. PDB files specified as query URL's from ftp servers are now handled correctly (provided the ftp server sends out the PDB file as chemical/x-pdb).
The default script for viewing single models on the NMR Model Selection page is now displayed in the help (press the [?] button after NMR Model Script, above the box). As explained in the help, this means you can paste it into the box and modify it.
A bug and a deficiency were fixed in the contact surfaces routines. A bug was fixed that prevented hydrogens from being excluded in ligand when requested. It was noted that unusual atoms, such as metals, were not being spacefilled in the receptor when within bonding distances. Hence, the "C/S" (carbon/sulfur) option was broadened to "C/S/X" (which click on to see more information).

August 3, 1999: beta-test version 0.992.

This version has been made capable of operating from the Protein Data Bank servers. The Protein Explorer decides it is on a PDB server when it finds itself being served from a directory path including the string "pdb/pe/". Therefore, this string should not be used in the installation path on non-PDB servers or local disks. When PE is on a PDB server, PDB files are fetched directly from the PDB cgi/export.cgi mechanism (http:///cgi/export.cgi/?comp=chime). Although the PE is being tested at the PDB, it will not likely be available on the public PDB beta server until September, nor on the production server until October or later (see acknowledgements).
In previous versions, molecules were always selected and loaded after entering the Explorer. This version offers automatic loading of pre-specified molecules upon entry. The molecules are specified with query parameters in the url, for example to fetch PDB ID 1d66 via Internet from a PDB mirror site,
www.umass.edu/microbio/chime/explorer/pe.htm?id=1d66
or to load a file from a local disk folder,
www.umass.edu/microbio/chime/explorer/pe.htm?id=c|/pdb/enzymes/1cbx.pdb&
The Comparator can be invoked by specifying two PDB ID's, for example
www.umass.edu/microbio/chime/explorer/pe.htm?id=1lck&id2=1b07
Detailed documentation is provided.
With the closing of the Brookhaven PDB site, the default source of PDB files via Internet has been changed to the former BNL PDB mirror at the Cambridge Crystallographic Data Centre, Cambridge UK. The three other former BNL PDB mirrors which currently provide the URL needed by PE to load molecules are also listed on the "change closest mirror" page (click the ? button next to the PDB ID slot on the "Load Molecule" page). Further information about the PDB, including PDB Lite access, is available at www.umass.edu/microbio/rasmol/pdblite.htm
The controls for generating surfaces and contact surfaces have been greatly expanded. Several internal checks have been implemented to avoid less informative results. A tutorial and documentation have been provided for the contact surfaces page. A preview snapshot of an exemplary contact surface is provided.
A new command to PE has been implemented, "tb". Prefixing a command with the word "tb" (short for "top + bottom") causes the command to be applied to both windows in the Comparator. An alias "sy" (short for "synch") was added which expands to "tb send mouse on", causing both windows to send mouse movements to each other (bidirectional mouse synchronization).
Earlier versions required Netscape 4.04 or later with javascript enabled and Chime 2 in order to enter the Explorer/Comparator. More thorough compatibility checking is now done, and more detailed instructions for achieving compatibility are provided. In this version, platforms other than Win32 and MacPPC are rejected (but an alternative solution is suggested), and java and cookies must be enabled before the client browser is allowed to start the Protein Explorer.

June 21, 1999: beta-test version 0.991.

PE 0.99 unnecessarily denied the use of long URL's to Macintoshes. PE now permits Macintoshes to use long URL's in "load" commands (>70 characters). Windows Chime 2.0.2 crashes Navigator with long URL's, so PE disallows such URL's for Windows.
Further improvements were made in sizing the command line slot and message box to fit various screen sizes.

June 16, 1999: beta-test version 0.99.

A list of features which make the PE easier to use and more powerful than RasMol has been added.
New control panels have been (partially) implemented for generating surfaces and contact surfaces colored by distance.
The tutorial has been partially drafted, and that part is included for what use it may be, incomplete though it is.
The bug which often prevented loading a molecule on the Macintosh has been fixed, I think. If any of these symptoms occur when you load a molecule on a Mac, let me know: the molecule fails to appear; error messages are generated in the message box; a permanent busy condition ensues. Also the [Clear] button now works to clear the message box on Macs.
A new preference controls whether molecules loaded are added to the 'Select previously loaded molecule' pick list.
The "show info" message is displayed upon loading a molecule.
A [Stereo] button has been added. You can set whether it toggles convergent or divergent stereo on the preferences screen.
The previous command can be recalled by typing "," (just the single character "comma"). "Comma" is the same as pushing the "Recall ^" button; "period" as pushing the "v" button.
A series of special "Commands to Protein Explorer" (as distinct from "Commands to Chime") have been implemented. All begin with a period followed by a single letter. These go directly to a desired control panel without a series of mouse clicks through intermediate panels. Press the [?] button next to the command line slot for the list.
The "NMR Model Script" is now remembered while you leave the "NMR Model Selection" control panel (including separately for the top and bottom molecules), but only within the session.
The command line slot, message box, and arrangement of the lower right frame now adjust in various ways to the size of the window to optimize visibility and usability. Best to resize the window BEFORE starting Explorer; else you need to Shift-Reload the lower right frame.

March 18, 1999: beta-test version 0.98.

Macintosh project folder. A bug was fixed which prevented the project folder mechanism from working on the Macintosh.
A menu delay was added so Chime's menu won't pop up unwanted on the Macintosh. Mac users should click on the "MDL" logo to get Chime's menu.

March 16, 1999: beta-test version 0.97.

Macintosh fixes. The following fixes were attempted for Macintoshes.

The [Synch] button in the Comparator is no longer present when used with a Macintosh because a bug in Chime 2.0 prevents it from working on Macintoshes (it works on Windows).
The frame(s) containing Chime should no longer have scrollbars.
After entering a command, the cursor should now return to the command slot. (If not, press Tab.)
When using Netscape 4.5 on a Mac, the preference "Add new messages at the bottom" defaults to checked. (If you have already used the Protein Explorer and entered the Preferences checklist, the settings present when you exited the Preferences checklist will not be changed.)

Netscape Toolbar eliminated. The window which opens for the Explorer/Comparator no longer has a toolbar, to discourage use of the [Back] and [Forward] buttons which don't work well in this context.
Atom Picking Reports Explained. A new preference has been added which, by default, attempts to explain/interpret the terse RasMol-style identifications reported when clicking on an atom.

February 4, 1999: beta-test version 0.96.

Purpose of the Protein Explorer. A new document entitled Purpose of the Protein Explorer has been provided with the rationale and some historical background.
Preferences. Several user-configurable preferences have been added. For example, you can specify that the initial view of newly loaded molecules not be spinning. Click on "Preferences" below the message box.
Command aliases. Command alias expansion has been implemented. For example, s l expands to select ligand. The list of aliases and replacements is user editable. Click on "Show aliases" below the message box for details.
Configurable project folder(s). It is possible to specify a "project folder" on your local hard disk. This means that all manually issued "load" and "script" commands will look for the referenced pdb and script files in the project folder. Click on "Set Project Folder" below the message box for details.
Add new messages at top or bottom. In Macintosh Navigator 4.5, the message textarea form element retains focus at the bottom of the message list, whereas in Windows and all previous versions for both platforms, focus remains at the top of the window. The default is to add new messages at the top of the window, so they are always visible for Windows. For Macintosh users of Navigator 4.5, this leaves the messages always out of view. Therefore a preference option has been provided which adds new messages at the bottom.
Force Ready. The Force Ready link under the message box now does what it says in one click. For example, resizing the window typically causes a permanent busy condition. Clicking once on Force Ready now cures this condition.
Shortening Chime-saved scripts. A new document was provided which describes how to shorten Chime-saved scripts. It is accessed from the "Set Project Folder" link below the message box.
Non-existent pdb/spt files. Attempting to load a non-existent PDB file or script from the local disk caused a permanent busy condition. The user is now alerted to click on "Force Ready" when necessary.
Structure message bug fixed. Using the menu to, for example, Color, Structure may cause the structure summary message list to be generated. These messages were not being handled properly, causing a fatal error. A similar condition occurred when "unable to allocate shade" color warning messages were emitted (for example after Color, Shapely). These messages now appear in the message box, and no fatal error is generated.

January 03, 1999: beta-test version 0.95.

Functions separated. The single upper right frame, which contained all controls, was getting too crowded and complicated. Therefore, PDB-file loading, NMR model selection, and Exploration have been separated onto different upper-right panels.
A new Message Control panel has been provided, accessed from the command-line/message-box panel in the lower right.
This version takes advantage of these enhancements in Chime version 2 (full release):

Multiple-model NMR files are now automatically detected and loaded accordingly. ("nmrpdb=1" is no longer needed in the embed tag for Chime.)
The following bug was fixed in Chime 2: in NMR mode, Chime 2-beta-4 was unable to run scripts from disk files.

Because this version depends on Chime 2's auto-detection of multiple-model NMR files, and the above bug fix, and since Chime 2 is now available for both Windows and Macintosh, Chime 1 is no longer supported.
Unscrambling of message order. The order of Chime's messages becomes scrambled when they are passed back to javascript for scripts of more than a dozen or so lines. This is true for Chime 1 and 2, and on both Windows and Macintosh. It is not a bug in Chime, but a peculiar interaction between Chime and Navigator which is not under the control of MDLI. The scrambling prevents javascript from obtaining script results unambiguously (for example atom counts following select commands, or the model count after loading an NMR file). A "workaround hook" was provided in Chime 2, namely, messages are now numbered. (See the RasMol email list history for '08 Nov 1998' for details.) Using these numbers, message order has now been unscrambled with a complicated javascript function (see unscramb.txt, unscramb.js and scrambld.txt; see also the description above under Design Features: Unscrambling).
Busy detection. A mechanism has been incorporated to prevent a script from being sent to Chime when it is busy processing the previous script, and to suggest that the user re-issue the request after waiting a few moments. The detection of busy-status for Chime requires the unscrambling mechanism mentioned above, and the addition to each script of a trailing "end of script" comment for detection in the returning message stream. See unscramb.txt.
Auto-detection of NMR model count. The unscrambling of message order (see item above) allows automatic determination of the number of models loaded when an NMR multiple-model file is loaded (see call to top.request_nmr_model_count() and render_view1() in loadit2.js). The entire process, which is tricky due to asynchrony between javascript and Chime, is described in a comment at the head of file cquery.js (Chime QUERY),which contains much of the relevant code.
New features on NMR Model Selection panel. Four new features were added. (i) The [Model] buttons can now step either forward ([Model+]) or backward ([-]). (ii) A new [Auto] button automatically steps through all models (or the models in the model list). Pressing the [Auto] button stops the progression, and reports the number of the model displayed when stopped. This allows one to determine the number of a selected model during the automatic stepping. (iii) A new Always show model black slot is provided. One model can remain displayed, in black, as a reference configuration, while stepping through other models with the [Model+][-] or [Auto] buttons. (iv) A new Model list slot is provided. Here one can list a series of model numbers, in any order. The [Model+][-], [Auto], and [All] buttons obey this series. Thus, one can step through any subset of the models in any desired order, or show any subset overlaid.
Mouse synchronization in the Comparator. A new [Synch] button, present only in the Comparator, forces the second molecule to follow mouse-directed movements of the first molecule. Thanks to Tim Maffett of MDLI who implemented this suggestion of mine in Chime 2.0.
Zoom convenience buttons. Although zooming can be done with the mouse (holding down the Shift key), the response is hypersensitive. Convenience buttons [Zoom^][v] were added which step the zoom either way in increments of 16% relative to the current size.
The default rendering of water is now spacefilled, rather than dot surfaces. The dot surfaces, and hiding water, are still available as steps on the cycle of the [Water] button.

October 18, 1998: beta-test version 0.92.

A slot has been provided which allows the user to specify script commands for any desired representation and color scheme for displaying NMR models. In the Protein Comparator, separate scripts can be specified for each molecule (top vs. bottom).
A number of minor bugs were fixed, and minor conveniences added, including a [Del] button to delete unwanted entries from the "Previously loaded PDB file" pick list.
Some non-obvious design features were documented, and information is provided about PE's use of cookies.

October 7, 1998: beta-test version 0.91.

The Macintosh does not allow PDB ID codes to be typed into the Browse slot. Therefore a separate slot has been provided for PDB ID's.
A bug which prevented items on the menu "Select previously loaded PDB file" from loading correctly on Macintoshes has (we hope) been fixed.
Water button now toggles water between hidden, dots, and spacefill. Bugs fixed: hetero button and water button now work in Comparator.
A bug which prevented the built-in Protein:DNA from being reported by the [?] button which reports "last file loaded" has been fixed.

October 4-5, 1998: beta-test version 0.9.

This is the first beta-test version, not yet an officially released version. It was offered to subscribers to the on October 4. On October 5, a bug in file-loading via Browse was fixed.