Accurate and Efficient Corrections for Missing Dispersion Interactions in Molecular Simulations

Michael R. Shirts*†
Department of Chemistry, Columbia University, New York, New York 10027
David L. Mobley†
Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143
John D. Chodera and Vijay S. Pande
Department of Chemistry, Stanford University, California 94305
J. Phys. Chem. B, 2007, 111 (45), pp 13052–13063
DOI: 10.1021/jp0735987
Publication Date (Web): October 19, 2007
Copyright © 2007 American Chemical Society
*

 Corresponding author. E-mail:  michael.shirts@columbia.edu

,
†

 These authors contributed equally to this work.

Abstract

In simulations, molecular dispersion interactions are frequently neglected beyond a cutoff of around 1 nm. In some cases, analytical corrections appropriate for isotropic systems are applied to the pressure and/or the potential energy. Here, we show that in systems containing macromolecules, either of these approaches introduce statistically significant errors in some observed properties; for example, the choice of cutoff can affect computed free energies of ligand binding to proteins by 1 to 2 kcal/mol. We review current methods for eliminating this cutoff-dependent behavior of the dispersion energy and identify some situations where they fail. We introduce two new formalisms, appropriate for binding free energy calculations, which overcome these failings, requiring minimal computational effort beyond the time required to run the original simulation. When these cutoff approximations are applied, which can be done after all simulations are completed, results are consistent across simulations run with different cutoffs. In many situations, simulations can be run with even shorter cutoffs than typically used, resulting in increased computational efficiency.

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History

  • Published In Issue November 15, 2007
  • Received May 10, 2007
    Revised August 22, 2007

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