DOCKING OF SMALL LIGANDS TO LOW-RESOLUTION AND THEORETICALLY PREDICTED RECEPTOR STRUCTURES

摘要

Methods are described that can utilize even low-resolution models of protein structures (e.g., as may be generated by stru cture prediction algorithms, for example, such as threading or ab initio folding algorithms) to predict the conformation of receptor-small ligand complexes. In preferred embodiments of t hese methods, only approximate, discretized models of both the small molecule ligand and receptor protein are used, and searched for the steric and quasi-chemical complementarity between the ligand and the receptor molecules. This averaging procedure allows for the compensation of numerous structural inaccuracies resulting from the theoretical predictions of the receptor structure. The best relative orientation of these two models was found to be obtained by an exhaustive scan over the rigid body's 6-dimensional translational and rotational degrees of freedom.