Tuesday, January 20, 2015

New manuscript: Predicting binding free energies in solution

Here is a new manuscript of mine that appeared on arXiv today.  It is a perspective paper, i.e. I mostly summarize what has already been published, and here is the abstract.

AbstractRecent predictions of absolute binding free energies of host-guest complexes in aqueous solution using electronic structure theory have been encouraging for some systems, while other systems remain problematic for others. In paper I summarize some of the many factors that could easily contribute 1-3 kcal/mol errors at 298 K: three-body dispersion effects, molecular symmetry, anharmonicity, spurious imaginary frequencies, insufficient conformational sampling, wrong or changing ionization states, errors in the solvation free energy of ions, and explicit solvent (and ion) effects that are not well-represented by continuum models. While the paper is primarily a synthesis of previously published work there are two new results: the adaptation of Legendre transformed free energies to electronic structure theory and a use of water clusters that maximizes error cancellation in binding free energies computed using explicit solvent molecules. While I focus on binding free energies in aqueous solution the approach also applies (with minor adjustments) to any free energy difference such as conformational free energy differences or activation free energies in any solvent.  

I am very interested in feedback on this paper and I'll wait a while with the submission to incorporate any suggestions.  There are several ways of providing feedback: comments below, comments on PubPeer (which allows for anonymous comments), and comments on Google docs using either the comment or editing tool.

This work is licensed under a Creative Commons Attribution 4.0

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