Molecular Docking Algorithm Based on Shape Complementarity Principles

PatchDock is an algorithm for molecular docking. The input is two molecules of any type: proteins, DNA, peptides, drugs. The output is a list of potential complexes sorted by shape complementarity criteria.

Short Overview:

PatchDock algorithm is inspired by object recognition and image segmentation techniques used in Computer Vision. Docking can be compared to assembling a jigsaw puzzle. When solving the puzzle we try to match two pieces by picking one piece and searching for the complementary one. We concentrate on the patterns that are unique for the puzzle element and look for the matching patterns in the rest of the pieces. PatchDock employs a similar technique. Given two molecules, their surfaces are divided into patches according to the surface shape. These patches correspond to patterns that visually distinguish between puzzle pieces. Once the patches are identified, they can be superimposed using shape matching algorithms. The algorithm has three major stages:

• Molecular Shape Representation - in this step we compute the molecular surface of the molecule. Next, we apply a segmentation algorithm for detection of geometric patches (concave, convex and flat surface pieces). The patches are filtered, so that only patches with 'hot spot' residues are retained.

• Surface Patch Matching - we apply a hybrid of the Geometric Hashing and Pose-Clustering matching techniques to match the patches detected in the previous step. Concave patches are matched with convex and flat patches with any type of patches.

• Filtering and Scoring - the candidate complexes from the previous step are examined. We discard all complexes with unacceptable penetrations of the atoms of the receptor to the atoms of the ligand. Finally, the remaining candidates are ranked according to a geometric shape complementarity score.

References:

• Duhovny D, Nussinov R, Wolfson HJ. Efficient Unbound Docking of Rigid Molecules. In Gusfield et al., Ed. Proceedings of the 2'nd Workshop on Algorithms in Bioinformatics(WABI) Rome, Italy, Lecture Notes in Computer Science 2452, pp. 185-200, Springer Verlag, 2002 [ PDF file ]
• Schneidman-Duhovny D, Inbar Y, Polak V, Shatsky M, Halperin I, Benyamini H, Barzilai A, Dror O, Haspel N, Nussinov R, Wolfson HJ. Taking geometry to its edge: fast unbound rigid (and hinge-bent) docking. Proteins. 2003 Jul 1; 52(1): 107-12. [ Abstract ] [ PDF file ]
• Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucl. Acids. Res. 33: W363-367, 2005.[ Full text ]