Qgui: A high-throughput interface for automated setup and analysis of free energy calculations and empirical valence bond simulations in biological systems

J Mol Graph Model. 2015 Jul:60:15-23. doi: 10.1016/j.jmgm.2015.05.007. Epub 2015 May 21.

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.

Keywords: Empirical valence bond; Free energies; Free energy perturbation; Linear interaction energy; Molecular dynamics; Q; Thermodynamic activation parameters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Automation
  • Calibration
  • Computer Graphics*
  • High-Throughput Screening Assays*
  • Models, Biological*
  • Models, Chemical*
  • Models, Molecular
  • Molecular Dynamics Simulation*
  • Monte Carlo Method
  • Reference Standards
  • Thermodynamics
  • Trypsin / chemistry
  • User-Computer Interface*

Substances

  • Trypsin