Incorporating the effect of ionic strength in free energy calculations using explicit ions

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. Journal of Computational Chemistry, 26 2: 115-122. doi:10.1002/jcc.20156


Author Donnini, S.
Mark, A. E.
Juffer, A. H.
Villa, A.
Title Incorporating the effect of ionic strength in free energy calculations using explicit ions
Journal name Journal of Computational Chemistry   Check publisher's open access policy
ISSN 0192-8651
Publication date 2005-01-01
Sub-type Article (original research)
DOI 10.1002/jcc.20156
Volume 26
Issue 2
Start page 115
End page 122
Total pages 8
Place of publication Hoboken
Publisher John Wiley & Sons Inc
Language eng
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. (C) 2004 Wiley Periodicals, Inc.
Keyword Chemistry, Multidisciplinary
molecular dynamics simulations
thermodynamic integration
free energy
ionic strength
triosephosphate isomerase inhibitors
Molecular-dynamics Simulations
Triosephosphate Isomerase
2-phosphoglycolate
Resolution
Catalysis
Binding
Protein
System
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 20 Sep 2007, 03:44:33 EST