Abstract:

A new method is presented to estimate the binding affinity for a given enzyme-ligand complex of known three-dimensional structure. This method, SCORE, uses empirical scoring function to describe the free energy of the binding process, which mainly accounts for enzyme-ligand interaction desolvation, and deformation effect A diverse training set of 66 crystalline complexes was analyzed by regressional statistics to obtained the final model. The model satisfactorily reproduced the dissociation constants of the tranining set with a standard deviation of 0.86 log units. A major innovation of this method is the introduction of atomic binding score This makes it a valuable tool for structure-based quantitative structure-activity relationship studies.

Key words: Drug design, Enzyme-ligand complex, Binding affinity, Structure-bsed quantitative structure-activity relationship