A new method is presented to estimate the binding affinity of a protein-ligand complex with known three-dimensional structure. The method, SCORE, uses an empirical scoring function to describe the binding free energy, which includes terms to account for van der Waals contact, metal-ligand bonding, hydrogen bonding, desolvation effect, and deformation penalty upon the binding process. The coefficients of each term are obtained by multivariate regressional analysis of a diverse training set of 170 protein-ligand complexes. The final scoring function reproduces the binding free energies of the whole training set with a cross-validated deviation of 6.3 kJ/mol. The predictive ability of the function is further tested by a set of 11 endothiapepsin complexes and the internal consistency of the function is demonstrated in a stepwise procedure named Evolutionary Test. A major innovation of this method is the introduction of an atomic binding score which allows the researcher to inspect and optimize the lead compound rationally in a structure-based drug design scheme.
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Received: 29 September 1998 / Accepted: 15 October 1998 / Published: 1 December 1998
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Wang, R., Liu, L., Lai, L. et al. SCORE: A New Empirical Method for Estimating the Binding Affinity of a Protein-Ligand Complex. J Mol Med 4, 379–394 (1998). https://doi.org/10.1007/s008940050096
- Keywords Protein-ligand complex
- Binding affinity
- Empirical scoring function
- Structure-based drug design