Why Morph? Many proteins perform their functions without major conformational changes, but for some proteins, major changes in secondary, tertiary, or quaternary structure are essential to function. In some cases, investigators have succeeded in obtaining empirically determined structures for a protein in two conformations. The challenge for visualization is then to be able to follow the movements of each portion between the two conformations. When the differences are small, simply toggling an image between the two states is adequate. David Richardson's MAGE (1992) is PC-compatible freeware which supports visual toggling between macromolecular conformations, and hundreds of kinemages take advantage of this capability. Here is an example from hemoglobin. However, when some of the conformational differences are large, toggling is not sufficient to allow one to follow the transition made by each portion as the image jumps between the two conformations. The purpose of morphing is to smooth the visual transition, making it easier to see the structural relationships between the two empirical conformations.

Linear Interpolation. 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, it is crucial to realize that while the interpolated intermediate conformations aid visualization, they are otherwise meaningless. Bond lengths and angles are unrealistic, domains may artifactually shrink, expand, or distort, and chains may even pass through each other during the interpolated movements. Linear interpolation morphing was first employed by Vonrhein, Schlauderer & Schultz (1995) to create movies of the results of substrate binding to nucleoside monophosphate kinases.

Plausible 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.

Morphing Methods For more details, see the morphing methods employed here.