Prediction of the binding energy for small molecules, peptides and proteins.
A fast and reliable evaluation of the binding energy from a single conformation of a molecular complex is an important practical task. Knowledge-based scoring schemes may not be sufficiently general and transferable, while molecular dynamics or Monte Carlo calculations with explicit solvent are too computationally expensive for many applications. Recently, several empirical schemes using finite difference Poisson-Boltzmann electrostatics to predict energies for particular types of complexes were proposed. Here, an improved empirical binding energy function has been derived and validated on three different types of complexes: protein-small ligand, protein-peptide and protein-protein. The function uses the boundary element algorithm to evaluate the electrostatic solvation energy. We show that a single set of parameters can predict the relative binding energies of the heterogeneous validation set of complexes with 2.5 kcal/mol accuracy. We also demonstrate that global optimization of the ligand and of the flexible side-chains of the receptor improves the accuracy of the evaluation.
Schapira
M
M
Skirball Institute of Biomolecular Medicine, Structural Biology, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA.
Totrov
M
M
Abagyan
R
R
D003198:Computer Simulation; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D008956:Models, Chemical; D008958:Models, Molecular; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012997:Solvents; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013500:Surface Tension; D013816:Thermodynamics
D017320:HIV Protease Inhibitors; D008024:Ligands; D046911:Macromolecular Substances; D010455:Peptides; D011506:Proteins; D012997:Solvents; D016333:HIV Protease