title: Thermodynamics and kinetics of ligand-protein binding studied with the weighted histogram analysis method and simulated annealing.
abstract: The thermodynamics of ligand-protein molecular recognition is investigated by the energy landscape approach for two systems: methotrexate(MTX)--dihydrofolate reductase(DHFR) and biotin-streptavidin. The temperature-dependent binding free energy profile is determined using the weighted histogram analysis method. Two different force fields are employed in this study: a simplified model of ligand-protein interactions and the AMBER force field with a soft core smoothing component, used to soften the repulsive part of the potential. The results of multiple docking simulations are rationalized from the shape of the binding free energy profile that characterizes the thermodynamics of the binding process.
authors.affiliation: Agouron Pharmaceuticals, Inc., La Jolla, CA 92037-1022, USA.
authors.forename: D
authors.initials: D
authors.lastname: Bouzida
authors.forename: S
authors.initials: S
authors.lastname: Arthurs
authors.forename: A B
authors.initials: AB
authors.lastname: Colson
authors.forename: S T
authors.initials: ST
authors.lastname: Freer
authors.forename: D K
authors.initials: DK
authors.lastname: Gehlhaar
authors.forename: V
authors.initials: V
authors.lastname: Larson
authors.forename: B A
authors.initials: BA
authors.lastname: Luty
authors.forename: P A
authors.initials: PA
authors.lastname: Rejto
authors.forename: P W
authors.initials: PW
authors.lastname: Rose
authors.forename: G M
authors.initials: GM
authors.lastname: Verkhivker
mesh_terms: D001710:Biotin / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D007700:Kinetics; D008024:Ligands; D008727:Methotrexate / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D009010:Monte Carlo Method; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012984:Software; D019809:Streptavidin / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D001710:Biotin; D019809:Streptavidin; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate