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Examples of Morphs
Morphs in Proteopedia
Morphs Elsewhere
Why Morph?
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| Toggling between the carbonmonoxy and deoxy conformations of heme in hemoglobin. (This is NOT a morph.) Convergent stereo snapshots from a Kinemage. (Stops after 25 cycles; reload this page to restart the toggling.) |
The purpose of molecular morphing is to smooth the visual transition between two molecular conformations, making it easier to see and understand the structural differences between them.
In contrast, predicting the actual trajectory through which a conformational change occurs is rarely, if ever, the goal of a morph.
Some proteins perform their functions without major conformational changes. On the other hand, some proteins must undergo major changes in secondary, tertiary, or quaternary structure in order to perform their functions. In quite a few cases, investigators have succeeded in obtaining empirically determined structures for a protein in two or more conformations. The challenge for visualization is then to be able to follow the changes in each region between the two conformations.
When the differences are small, simply toggling an image between the two states is adequate. David Richardson's MAGE[3], first available in 1992[4] supports visual toggling between macromolecular conformations. Hundreds of interactive molecular structure tutorials called kinemages take advantage of this capability. At the right are snapshots of hemoglobin toggled in MAGE. (MAGE is available in java applet form, and is an option for molecular displays in Proteopedia[5].)
On the other hand, when the conformational changes are large, toggling between two very different conformations leaves the eye unable to grasp what has happened. This is when morphing is useful for seeing and understanding the differences between conformations. A dramatic example is Recoverin.
History of Macromolecular Morphing
Perhaps the first macromolecular morph was in 1995 by Vonrhein, Schlauderer & Schultz[6]
who animated substrate binding to nucleoside monophosphate kinases using linear interpolation.
In 1998, or shortly before, Mark Gerstein, Werner Krebs and their team at Yale University released a Morph Server that made it easy to obtain chemically possible morphs. They and others have subsequently used the results of this server to classify molecular movements, and to develop an impressive Database of Macromolecular Movements, molmovdb.org, with research-quality analysis tools and multiple visualization options.
In 1998, encouraged by Joel Sussman, Eric Martz released a Protein Morpher website[7] which displayed morphs of several molecules using the MDL Chime browser plugin[4]. A few years later, he incorporated morph animation capability into Protein Explorer, where he implemented a number of additional morphs.
Visualizing Morphs
(to be added)
Morphing Methods
Linear Interpolation
In this method, a series of intermediate models are created in which each atom moves in a straight line from is initial position to its final position. This type of morphing is relatively easy to perform, and often suffices, but also has a number of limitations. When animated, the interpolated intermediate conformations often greatly help in visualizing the differences between the initial and final empirical models. However, otherwise they are otherwise meaningless. Bond lengths and angles become unrealistic, domains may artifactually shrink, expand, or distort, and chains may even pass through each other during the interpolated movements. When there are substantial changes in secondary structure or large movements of domains, linear interpolation becomes unsatisfactory.
A toggler is implemented here for Recoverin. Despite such features as the ability to highlight any arbitrary range of residues, it remains too difficult to follow the changes in secondary and tertiary structure during the large jumps in position. Consequently, a series of intermediate conformations were generated by linear interpolation of alpha carbon positions. This backbone trace "morph" makes it much easier to follow the relations between the two empirical conformations. However, Linear interpolation morphing was first employed by Vonrhein, Schlauderer & Schultz (1995) to create movies of the results of substrate binding to nucleoside monophosphate kinases.
Chemically Possible Intermediates
Plausible intermediate conformations have been calculated by Mark Gerstein and Werner Krebs at Yale University, using a combination of linear interpolation and molecular dynamics. Gerstein has generously made his interpolation data available, and in some cases they are here displayed in this Chime-based Protein Morpher interface. At the Gerstein Lab Homepage you will find movies of plausible morphs in animated GIF's, Quicktime, and VRML. Another source of "chemically reasonable" morphs is the Biomolecular Morphing site by Gerard J. Kleywegt at Uppsala University, Sweden.
References, LInks, and Notes
- ↑ Database of Macromolecular Movements with Associated Tools for Flexibility and Geometric Analysis, molmovdb.org, developed by Mark Gerstein and coworkers at Yale University, USA.
- ↑ Animations in Protein Explorer developed by Eric Martz at the University of Massachusetts, Amherst, USA.
- ↑ Kinemages by David and Jane Richardson, Duke University, USA.
- ↑ 4.0 4.1 History of Macromolecular Visualization
- ↑ For sample pages that use the MAGE applet in Proteopedia, see Hemoglobin and Ribulose-1,5-bisphosphate carboxylase/oxygenase
- ↑ Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases. Vonrhein, Schlauderer & Schultz, Structure 3:483-90, 1995. PubMed 7663945
- ↑ The Protein Morpher website is difficult to view today because it requires obsolete software, and has not been maintained. It was later superceded by the ability of Protein Explorer to display morphs (morphs.proteinexplorer.org).
