title: Empirical scoring functions: I. The development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes.
abstract: 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.
authors.affiliation: Proteus Molecular Design Ltd., Macclesfield, Cheshire, U.K.
authors.forename: M D
authors.initials: MD
authors.lastname: Eldridge
authors.forename: C W
authors.initials: CW
authors.lastname: Murray
authors.forename: T R
authors.initials: TR
authors.lastname: Auton
authors.forename: G V
authors.initials: GV
authors.lastname: Paolini
authors.forename: R P
authors.initials: RP
authors.lastname: Mee
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D010450:Endopeptidases / Q000737:chemistry*; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D012044:Regression Analysis; D012984:Software; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D010450:Endopeptidases