The morph server: a standardized system for analyzing and visualizing macromolecular motions in a database framework

The number of solved structures of macromolecules that have the same fold a nd thus exhibit some degree of conformational variability is rapidly increa sing, It is consequently advantageous to develop a standardized terminology for describing this variability and automated systems for processing prote in structures in different conformations, We have developed such a system a s a 'front-end' server to our database of macromolecular motions. Our syste m attempts to describe a protein motion as a rigid-body rotation of a small 'core' relative to a larger one, using a set of hinges. The motion is plac ed in a standardized coordinate system so that all statistics between any t wo motions are directly comparable. We find that while this model can accom modate most protein motions, it cannot accommodate all; the degree to which a motion can be accommodated provides an aid in classifying it. Furthermor e, we perform an adiabatic mapping (a restrained interpolation) between eve ry two conformations. This gives some indication of the extent of the energ etic barriers that need to be surmounted in the motion, and as a by-product results in a 'morph movie'. We make these movies available over the Web to aid in visualization, Many instances of conformational variability occur b etween proteins with somewhat different sequences, We can accommodate these differences in a rough fashion, generating an 'evolutionary morph', Users have already submitted hundreds of examples of protein motions to our serve r, producing a comprehensive set of statistics. So far the statistics show that the median submitted motion has a rotation of similar to 10 degrees an d a maximum C alpha displacement of 17 Angstrom. Almost all involve at leas t one targe torsion angle change of >140 degrees. The server is accessible at http://bioinfo.mbb.yale.edu/MolMovDB.