Empirical scoring functions: I. 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 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.
Eldridge
M D
MD
Proteus Molecular Design Ltd., Macclesfield, Cheshire, U.K.
Murray
C W
CW
Auton
T R
TR
Paolini
G V
GV
Mee
R P
RP
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
D008024:Ligands; D011506:Proteins; D010450:Endopeptidases