Patent ID: 7065453
Filing Date: 2006-06-20
Classification: C07K,G16C

Abstract:
1. A computer-aided method of docking a ligand to a protein so as to determine ligand conformations likely to bind to said protein, said method comprising: performing a pre-docking conformational search and generating multiple solution conformations of a ligand therefrom; generating a binding site image of a protein, said binding site image comprising multiple hot spots; matching hot spots of the binding site image to atoms in at least one conformation of the multiple solution conformations of the ligand to initially position said at least one conformation of said ligand as a rigid body into said binding site so as to obtain at least one position of the ligand relative to the protein in a protein-ligand complex; optimizing the at least one position of the ligand while allowing translation, orientation and rotatable bonds of the ligand to vary, and while holding the protein fixed; calculating a score for the optimized position of the ligand using one or more potential functions; selecting one or more optimized ligand positions based on said score; wherein said matching comprises: wherein said determining the unique rigid body transformation comprises determining the unique rigid body transformation that minimizes: where: I(R,T)=rms deviation between a j H A R=a 3×3 rotation matrix; and T=a translation vector.