title: Protein-ligand binding free energy calculation by the Smooth Reaction Path Generation (SRPG) Method.
abstract: We developed a new molecular dynamics simulation method for protein-ligand binding free energy calculation in an explicit water model. This method consists of three steps: (1) generation of a compound dissociation path starting from a stable protein-compound complex structure, (2) calculation of the free energy surface along the dissociation path, and (3) calculation of the free energy surface of a small area around the protein-compound complex structure, which is a free energy minimum. The protein-compound binding free energy is estimated from the information obtained by the above three steps. This method was applied to a small system, a 18-crown-6 ether with its ligand ion, and a realistic system consisting of a target protein with its inhibitor. This approximation worked well; the protein-inhibitor dissociation was successfully performed, and the binding free energies were calculated.
authors.affiliation: Biomedicinal Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan. y-fukunishi@aist.go.jp
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Fukunishi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mitomo
authors.forename: Haruki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D001710:Biotin / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D043844:Crown Ethers / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D019809:Streptavidin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D043844:Crown Ethers; D008024:Ligands; D011506:Proteins; D001710:Biotin; D019809:Streptavidin