A Simple QM/MM Approach for Capturing Polarization Effects in Protein-Ligand Binding Free Energy Calculations

Journal article


Publication Details

Author(s): Beierlein F, Michel J, Essex J
Journal: Journal of Physical Chemistry B
Publisher: American Chemical Society
Publication year: 2011
Volume: 115
Pages range: 4911-4926
ISSN: 1520-6106
eISSN: 1520-5207


Abstract

We present a molecular simulation protocol to compute free energies of binding, which combines a QM/MM correction term with rigorous classical free energy techniques, thereby accounting for electronic polarization effects. Relative free energies of binding are first computed using classical force fields, Monte Carlo sampling, and replica exchange thermodynamic integration. Snapshots of the configurations at the end points of the perturbation are then subjected to DFT-QM/MM single-point calculations using the B3LYP functional and a range of basis sets. The resulting quantum mechanical energies are then processed using the Zwanzig equation to give free energies incorporating electronic polarization. Our approach is conceptually simple and does not require tightly coupled QM and MM software. The method has been validated by calculating the relative free energies of hydration of methane and water and the relative free energy of binding of two inhibitors of cyclooxygenase-2. Closed thermodynamic cycles are obtained across different pathways, demonstrating the correctness of the technique, although significantly more sampling is required for the protein$-$ligand system. Our method offers a simple and effective way to incorporate quantum mechanical effects into computed free energies of binding.


FAU Authors / FAU Editors

Beierlein, Frank Dr.
Computer-Chemie-Centrum


Additional Organisation
Exzellenz-Cluster Engineering of Advanced Materials


How to cite

APA:
Beierlein, F., Michel, J., & Essex, J. (2011). A Simple QM/MM Approach for Capturing Polarization Effects in Protein-Ligand Binding Free Energy Calculations. Journal of Physical Chemistry B, 115, 4911-4926. https://dx.doi.org/10.1021/jp109054j

MLA:
Beierlein, Frank, Julien Michel, and Jonathan Essex. "A Simple QM/MM Approach for Capturing Polarization Effects in Protein-Ligand Binding Free Energy Calculations." Journal of Physical Chemistry B 115 (2011): 4911-4926.

BibTeX: 

Last updated on 2019-14-03 at 12:39