The goal of this proposal is to construct a working database of protein motions. This database will be made into a publicly accessible WWW community resource, of general use to the molecular biophysics community. It will meet the needs of researchers trying to understand the principles of protein structure and function (since motions are often the link between structure and function). The database will be associated with a classification of protein motions, based on the packing at mobile interfaces. The construction of this database has recently become feasible because of a number of developments: the great increase in the number of solved protein structures, the creation of an infrastructure of linked biological databases, and work showing how packing can be used to rationalize mechanisms for protein motions. The development of the database will proceed in two phases with two objectives in each phase (one computational and the other biological). The principal objective in the first phase will be to establish a working, prototype database of protein motions. Motions in this database will initially be arranged hierarchically in terms of size (i.e. fragment, domain, and subunit) and then packing. The packing classification will depend on whether or not the motion involves sliding over a continuously maintained interface. To achieve the first objective it will be necessary to develop a standardized nomenclature and conceptual- information model for protein motions. This will include information such as the number of hinges, the magnitude of the rigidbody rotation, and the number and size of the mobile interfaces. Building upon the framework established in the first phase, the second phase of the project will expand the database and associated motions classification. The goal will be to have an entry for every known protein motion. In addition, "inferred motions," in sequence and structure homologues of a protein with known motion, will also be included. To han dle the large amount of data this will involve analyzing and to help "populate" the database, an automatic conformation comparison tool will be developed. This will rapidly align and compare two arbitrary protein conformations, identifying rigid core regions, flexible hinges, interface packing differences, and so forth. It will also determine whether these structures have any sequence or structure homologues that share their motion. The expansion of the database will require a more sophisticated structure for describing the relationships between motions and a more detailed motion classification scheme than the size-packing hierarchy initially used. The motions classification will be expanded through detailed geometric analysis and calculation, principally focusing on the packing at mobile interfaces.
