Efficient Algorithms for 3D Protein Substructure Identification

Identifying the location of binding sites on proteins is of fundamental importance for a wide range of applications including molecular docking, de novo drug design, structure identification and comparison of functional sites. Structural genomics projects are beginning to produce protein structures with unknown functions. Therefore, efficient methods are required if all these structures are to be properly annotated. Identifying the interface between two interacting proteins provides important clues to the function of a protein and can reduce the search space required by docking algorithms to predict the structures of complexes. Here we develop a software package for identifying similar 3D protein substructures via direct comparison of 3D structures. Results: We develop an efficient heuristic algorithm for finding protein 3D substructures in a 3D protein structure that are similar to a given 3D protein substructure. This algorithm can also be used for searching a database of protein 3D structures. We also design an algorithm for finding similar 3D substructures from two given 3D protein structures. Our approach is to directly compare the substructures by computing a rigid transformation such that the distance between a pair of corresponding points in the matched substructures is bounded by a given value d. We propose an efficient local search heuristic approach for finding an approximate rigid transformation. We implement the algorithms and produce a software package that works well in practice. Experiments show that our software package can find pairs of similar 3D substructures in reasonable time. We also provide graphical interface to allow users to view the pairs of 3D protein substructures from different angles.