Enhanced configurational sampling in binding free-energy calculations
Enhanced configurational sampling in binding free-energy calculations
The newly developed method of replica-exchange thermodynamic integration (RETI) was tested and compared with finite-difference thermodynamic integration (FDTI) on the calculation of the relative binding free energies of halides to a calix[4]pyrrole derivative. The calculation was challenging, because the dimethylsulfoxide solvent was contaminated by small amounts of water. The lambda-swap move of RETI enabled more-complete sampling of the solvents and produced relative binding free energies that included the effect of the fluoride's higher affinity for water. In addition, the lambda-swap move increased the quality of the configurational sampling of the host, because the system was able to escape from local minima. The results demonstrate that the sampling of RETI is superior to that of FDTI, at no additional computational expense.
difference, thermodynamic integration, monte-carlo simulations, replica-exchange method, thrombin inhibition, potential functions, sh2domain, hydration, ligands, water, calixpyrrole
13711-13718
Woods, Christopher J.
54c21a03-755f-4977-aa2c-72c1b073e734
Essex, Jonathon W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
King, Michael A.
60520a12-4a45-435b-98bb-420eff76ab34
11 December 2003
Woods, Christopher J.
54c21a03-755f-4977-aa2c-72c1b073e734
Essex, Jonathon W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
King, Michael A.
60520a12-4a45-435b-98bb-420eff76ab34
Woods, Christopher J., Essex, Jonathon W. and King, Michael A.
(2003)
Enhanced configurational sampling in binding free-energy calculations.
The Journal of Physical Chemistry B, 107 (49), .
(doi:10.1021/jp036162+).
Abstract
The newly developed method of replica-exchange thermodynamic integration (RETI) was tested and compared with finite-difference thermodynamic integration (FDTI) on the calculation of the relative binding free energies of halides to a calix[4]pyrrole derivative. The calculation was challenging, because the dimethylsulfoxide solvent was contaminated by small amounts of water. The lambda-swap move of RETI enabled more-complete sampling of the solvents and produced relative binding free energies that included the effect of the fluoride's higher affinity for water. In addition, the lambda-swap move increased the quality of the configurational sampling of the host, because the system was able to escape from local minima. The results demonstrate that the sampling of RETI is superior to that of FDTI, at no additional computational expense.
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Published date: 11 December 2003
Keywords:
difference, thermodynamic integration, monte-carlo simulations, replica-exchange method, thrombin inhibition, potential functions, sh2domain, hydration, ligands, water, calixpyrrole
Identifiers
Local EPrints ID: 20107
URI: http://eprints.soton.ac.uk/id/eprint/20107
ISSN: 1520-5207
PURE UUID: d664b7a3-f20e-4f3e-87c5-43ddd566d16a
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Date deposited: 23 Feb 2006
Last modified: 16 Mar 2024 02:45
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Author:
Christopher J. Woods
Author:
Michael A. King
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