SPECIFICITY QUANTIFICATION OF BIOMOLECULAR RECOGNITION AND ITS APPLICATION FOR DRUG DISCOVERY

摘要

A novel scoring function called SPA takes account of both specificity and affinity of highly efficient and specific protein-ligand binding. The method to develop SPA is based on the funneled energy landscape theory and employs affinity and specificity of biomolecular interactions. The quantified specificity of the native protein-ligand complex, which discriminates against “non-native” binding modes, and the affinity prediction are simultaneously optimized during the development. SPA is obtained by maximizing the specificity and affinity prediction of a large training set of “native” protein-ligand complexes with known structures and affinities. SPA can be employed to discriminate drugs from the diversity set, or to discriminate selective drugs from non-selective drugs. The remarkable performance of SPA makes it promising to be implemented in the docking software and widely applied in virtual screening for seeking the lead compounds.