Jump to main content
Jump to site search

Issue 44, 2016
Previous Article Next Article

Calculating binding free energies of host–guest systems using the AMOEBA polarizable force field

Author affiliations

Abstract

Molecular recognition is of paramount interest in many applications. Here we investigate a series of host–guest systems previously used in the SAMPL4 blind challenge by using molecular simulations and the AMOEBA polarizable force field. The free energy results computed by Bennett's acceptance ratio (BAR) method using the AMOEBA polarizable force field ranked favorably among the entries submitted to the SAMPL4 host–guest competition [Muddana, et al., J. Comput.-Aided Mol. Des., 2014, 28, 305–317]. In this work we conduct an in-depth analysis of the AMOEBA force field host–guest binding thermodynamics by using both BAR and the orthogonal space random walk (OSRW) methods. The binding entropy–enthalpy contributions are analyzed for each host–guest system. For systems of inordinate binding entropy–enthalpy values, we further examine the hydrogen bonding patterns and configurational entropy contribution. The binding mechanism of this series of host–guest systems varies from ligand to ligand, driven by enthalpy and/or entropy changes. Convergence of BAR and OSRW binding free energy methods is discussed. Ultimately, this work illustrates the value of molecular modelling and advanced force fields for the exploration and interpretation of binding thermodynamics.

Graphical abstract: Calculating binding free energies of host–guest systems using the AMOEBA polarizable force field

Back to tab navigation
Please wait while Download options loads

Supplementary files

Publication details

The article was received on 14 Apr 2016, accepted on 19 May 2016 and first published on 19 May 2016


Article type: Paper
DOI: 10.1039/C6CP02509A
Citation: Phys. Chem. Chem. Phys., 2016,18, 30261-30269
  •   Request permissions

    Calculating binding free energies of host–guest systems using the AMOEBA polarizable force field

    D. R. Bell, R. Qi, Z. Jing, J. Y. Xiang, C. Mejias, M. J. Schnieders, J. W. Ponder and P. Ren, Phys. Chem. Chem. Phys., 2016, 18, 30261
    DOI: 10.1039/C6CP02509A

Search articles by author