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Incorporating the effect of ionic strength in free energy calculations using explicit ions
Article first published online: 6 DEC 2004
DOI: 10.1002/jcc.20156
Copyright © 2004 Wiley Periodicals, Inc.
1096-987X/asset/cover.gif?v=1&s=4429aac2462ebd499c13b3d7fe983679c5767778 "Journal of Computational Chemistry")
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How to Cite
Donnini, S., Mark, A. E., Juffer, A. H. and Villa, A. (2005), Incorporating the effect of ionic strength in free energy calculations using explicit ions. J. Comput. Chem., 26: 115–122. doi: 10.1002/jcc.20156
Publication History
- Issue published online: 6 DEC 2004
- Article first published online: 6 DEC 2004
- Manuscript Accepted: 20 AUG 2004
- Manuscript Received: 10 MAY 2004
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Keywords:
- molecular dynamics simulations;
- thermodynamic integration;
- free energy;
- ionic strength;
- triosephosphate isomerase inhibitors
Abstract
The incorporation of explicit ions to mimic the effect of ionic strength or to neutralize the overall charge on a system in free energy calculations using molecular dynamics simulations is investigated. The difference in the free energy of hydration between two triosephosphate isomerase inhibitors calculated at five different ion concentrations is used as an example. We show that the free energy difference can be highly sensitive to the presence of explicit ions even in cases where the mutation itself does not involve a change in the overall charge. The effect is most significant if the molecule carries a net charge close to the site mutated. Furthermore, it is shown that the introduction of a small number of ions can lead to very severe sampling problems suggesting that in practical calculations convergence can best be achieved by incorporating either no counterions or by simulating at high ionic strength to ensure sufficient sampling of the ion distribution. © 2004 Wiley Periodicals, Inc. J Comput Chem 26: 115–122, 2005