COMPUTER METHOD UTILIZING FREE ENERGY CALCULATIONS FOR LIGAND DESIGN AND THE PREDICTION OF BINDING TARGETS

摘要

A kind of computer based method combines target protein or other macromoleculars for identification. More particularly it relates to include algorithm, it is intended to which prediction combines target protein. The algorithm, referred to as Woolford, it is desirable that know the protein of high resolution structure, but not location aware or identity natural attachment site or ligand. It is identified and classifies in conjunction with target protein, according to the affinities of their anticipated optimal set. Combining target can be located at protein surface or become exposed inner surface due to local expansion, conformation change, subunit dissociation or other events at that. Entire albumen map bindings may be according to the atom of its component. Once combining target is identified, optimal ligand design and gradually build up, by the way that single atom is added, that is replenished in structure and the effectively target of the selection. The algorithm is expected to have important application in Structure-ba sed drug design, because it allows: 1) identification combines target protein; 2) if identification additional object main target is known; 3) target of ligand molecule and best combination affinity is designed; With 4) refining lead compound, pass through the position of definition and the best combination affinity of property chemical group.