EMPIRICAL SCORING FUNCTIONS .1. THE DEVELOPMENT OF A FAST EMPIRICAL SCORING FUNCTION TO ESTIMATE THE BINDING-AFFINITY OF LIGANDS IN RECEPTOR COMPLEXES

This paper describes the development of a simple empirical scoring fun ction designed to estimate the free energy of binding for a protein-li gand complex when the 3D structure of the complex is known pr can be a pproximated. The function uses simple contact terms to estimate lipoph ilic and metal-ligand binding contributions, a simple explicit form fo r hydrogen bonds and a term which penalises flexibility. The coefficie nts of each term are obtained using a regression based on 82 ligand-re ceptor complexes for which the binding affinity is known. The function reproduces the binding affinity of the complexes with a cross-validat ed error of 8.68 kJ/mol. Tests on internal consistency indicate that t he coefficients obtained are stable to changes in the composition of t he training set. The function is also tested on two test sets containi ng a further 20 and 10 complexes, respectively. The deficiencies of th is type of function are discussed and it is compared to approaches by other workers.