Studying Macromolecular Motions in a Database Framework: From Structure to Sequence

Abstract

We describe database approaches taken in our lab to the study of protein and nucleic acid motions. We have developed a database of macromolecular motions, which is accessible on the World Wide Web with an entry point at http://bioinfo.mbb.yale.edu/MolMovDB. This attempts to systematize all instances of macromolecular movement for which there is at least some structural information. At present it contains detailed descriptions of more than 100 motions, most of which are of proteins. Protein motions are further classified hierarchically into a limited number of categories, first on the basis of size (distinguishing between fragment, domain, and subunit motions) and then on the basis of packing. Our packing classification divides motions into various categories (shear, hinge, other) depending on whether or not they involve sliding over a continuously maintained and tightly packed interface. We quantitatively systematize the description of packing through the use of Voronoi polyhedra and Delaunay triangulation. In addition to the packing classification, the database provides some indication about the evidence behind each motion (i.e. the type of experimental information or whether the motion is inferred based on structural similarity) and attempts to describe many aspects of a motion in terms of a standardized nomenclature (e.g. the maximum rotation, the residue selection of a fixed core, etc). Currently, we use a standard relational design to implement the database. However, the complexity and heterogeneity of the information kept in the database makes it an ideal application for an object-relational approach, and we are moving it in this direction. The database, moreover, incorporates innovative Internet cooperatively features that allow authorized remote experts to serve as database editors. The database also contains plausible representations for motion pathways, derived from restrained 3D interpolation between known endpoint conformations. These pathways can be viewed in a variety of movie formats, and the database is associated with a server that can automatically generate these movies from submitted coordinates. Based on the structures in the database we have developed sequence patterns for linkers and flexible hinges and are currently using these for the annotation of genome sequence data.