A semiempirical free energy force field with charge-based desolvation.
The authors describe the development and testing of a semiempirical free energy force field for use in AutoDock4 and similar grid-based docking methods. The force field is based on a comprehensive thermodynamic model that allows incorporation of intramolecular energies into the predicted free energy of binding. It also incorporates a charge-based method for evaluation of desolvation designed to use a typical set of atom types. The method has been calibrated on a set of 188 diverse protein-ligand complexes of known structure and binding energy, and tested on a set of 100 complexes of ligands with retroviral proteases. The force field shows improvement in redocking simulations over the previous AutoDock3 force field.
Huey
Ruth
R
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92102, USA.
Morris
Garrett M
GM
Olson
Arthur J
AJ
Goodsell
David S
DS
D000465:Algorithms; D030562:Databases, Protein; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry; D006860:Hydrogen Bonding; D008024:Ligands; D008432:Mathematical Computing; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012984:Software; D055672:Static Electricity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D017320:HIV Protease Inhibitors; D008024:Ligands; D011506:Proteins; D014867:Water; D016333:HIV Protease