title: Calculation of the relative change in binding free energy of a protein-inhibitor complex.
abstract: By means of a thermodynamic perturbation method implemented with molecular dynamics, the relative free energy of binding was calculated for the enzyme thermolysin complexed with a pair of phosphonamidate and phosphonate ester inhibitors. The calculated difference in free energy of binding was 4.21 +/- 0.54 kilocalories per mole. This compares well with the experimental value of 4.1 kilocalories per mole. The method is general and can be used to determine a change or "mutation" in any system that can be suitably represented. It is likely to prove useful for protein and drug design.
mesh_terms: D000577:Amides / Q000494:pharmacology; D004952:Esters / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D063065:Organophosphonates / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D013820:Thermolysin / Q000037:antagonists & inhibitors*; D014961:X-Ray Diffraction
chemical_list: D000577:Amides; D004952:Esters; D009842:Oligopeptides; D063065:Organophosphonates; D013820:Thermolysin