title: Qgui: A high-throughput interface for automated setup and analysis of free energy calculations and empirical valence bond simulations in biological systems.
abstract: Structural information and activity data has increased rapidly for many protein targets during the last decades. In this paper, we present a high-throughput interface (Qgui) for automated free energy and empirical valence bond (EVB) calculations that use molecular dynamics (MD) simulations for conformational sampling. Applications to ligand binding using both the linear interaction energy (LIE) method and the free energy perturbation (FEP) technique are given using the estrogen receptor (ERα) as a model system. Examples of free energy profiles obtained using the EVB method for the rate-limiting step of the enzymatic reaction catalyzed by trypsin are also shown. In addition, we present calculation of high-precision Arrhenius plots to obtain the thermodynamic activation enthalpy and entropy with Qgui from running a large number of EVB simulations.
authors.affiliation: The Centre for Theoretical and Computational Chemistry, Department of Chemistry, University of Tromsø, N9037 Tromsø, Norway.
authors.forename: Geir Villy
authors.initials: GV
authors.lastname: Isaksen
authors.affiliation: The Centre for Theoretical and Computational Chemistry, Department of Chemistry, University of Tromsø, N9037 Tromsø, Norway.
authors.forename: Tor Arne Heim
authors.initials: TA
authors.lastname: Andberg
authors.affiliation: Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Box 596, S-75124 Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Åqvist
authors.affiliation: The Centre for Theoretical and Computational Chemistry, Department of Chemistry, University of Tromsø, N9037 Tromsø, Norway. Electronic address: bjorn-olav.brandsdal@uit.no.
authors.forename: Bjørn Olav
authors.initials: BO
authors.lastname: Brandsdal
mesh_terms: D000818:Animals; D001331:Automation; D002138:Calibration; D003196:Computer Graphics; D057166:High-Throughput Screening Assays; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D012015:Reference Standards; D013816:Thermodynamics; D014357:Trypsin / Q000737:chemistry; D014584:User-Computer Interface
chemical_list: D014357:Trypsin
keywords: Empirical valence bond; Free energies; Free energy perturbation; Linear interaction energy; Molecular dynamics; Q; Thermodynamic activation parameters