Molecular modeling annual

, Volume 4, Issue 12, pp 379–394

SCORE: A New Empirical Method for Estimating the Binding Affinity of a Protein-Ligand Complex

  • Renxiao Wang
  • Liang Liu
  • Luhua Lai
  • Youqi Tang
Full Paper

DOI: 10.1007/s008940050096

Cite this article as:
Wang, R., Liu, L., Lai, L. et al. J Mol Med (1998) 4: 379. doi:10.1007/s008940050096

Abstract

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.

Keywords Protein-ligand complexBinding affinityEmpirical scoring functionStructure-based drug design

Copyright information

© Springer-Verlag Heidelberg 1998

Authors and Affiliations

  • Renxiao Wang
    • 1
  • Liang Liu
    • 1
  • Luhua Lai
    • 1
  • Youqi Tang
    • 1
  1. 1.Institute of Physical Chemistry, Peking University, Beijing 100871, P.R.China. Tel: +86-10-62751490; Fax:   +86-10-62751725. E-mail: lai@ipc.pku.edu.cnCN