Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes

J Comput Aided Mol Des. 1997 Sep;11(5):425-45. doi: 10.1023/a:1007996124545.


This paper describes the development of a simple empirical scoring function designed to estimate the free energy of binding for a protein-ligand complex when the 3D structure of the complex is known or can be approximated. The function uses simple contact terms to estimate lipophilic and metal-ligand binding contributions, a simple explicit form for hydrogen bonds and a term which penalises flexibility. The coefficients of each term are obtained using a regression based on 82 ligand-receptor complexes for which the binding affinity is known. The function reproduces the binding affinity of the complexes with a cross-validated error of 8.68 kJ/mol. Tests on internal consistency indicate that the coefficients obtained are stable to changes in the composition of the training set. The function is also tested on two test sets containing a further 20 and 10 complexes, respectively. The deficiencies of this type of function are discussed and it is compared to approaches by other workers.

MeSH terms

  • Binding Sites
  • Drug Design*
  • Endopeptidases / chemistry*
  • Ligands*
  • Protein Binding*
  • Proteins / chemistry*
  • Regression Analysis
  • Software
  • Thermodynamics


  • Ligands
  • Proteins
  • Endopeptidases