The parameterization and validation of generalized born models using the pairwise descreening approximation
The parameterization and validation of generalized born models using the pairwise descreening approximation
Generalized Born Surface Area (GBSA) models for water using the Pairwise Descreening Approximation (PDA) have been parameterized by two different methods. The first method, similar to that used in previously reported parameterizations, optimizes all parameters against the experimental free energies of hydration of organic molecules. The second method optimizes the PDA parameters to compensate only for systematic errors of the PDA. The best models are compared to Poisson-Boltzmann calculations and applied to the computation of potentials of mean force (PMFs) for the association of various molecules. PMFs present a more rigorous test of the ability of a solvation model to correctly reproduce the screening of intermolecular interactions by the solvent, than its accuracy at predicting free energies of hydration of small molecules. Models derived with the first method are sometimes shown to fail to compute accurate potentials of mean force because of large errors in the computation of Born radii, while no such difficulties are observed with the second method. Furthermore, accurate computation of the Born radii appears to be more important than good agreement with experimental free energies of solvation. We discuss the source of errors in the potentials of mean force and suggest means to reduce them. Our findings suggest that Generalized Born models that use the Pairwise Descreening Approximation and that are derived solely by unconstrained optimization of parameters against free energies of hydration should be applied to the modeling of intermolecular interactions with caution.
continuum solvation, generalized born, pairwise descreening
approximation, potentials of mean force, amino acid side chainacid side-chains, free-energy, mean force, atomic charges, computer-simulations, molecular mechanics, dielectric medium, solventmodels, nucleic-acids, solvation
1760-1770
Michel, Julien
3dfda20a-a6fa-4214-8c7d-578f550b9ad7
Taylor, Richard D.
141004d4-95a6-44f1-93ce-ca36c1b34d61
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
15 November 2004
Michel, Julien
3dfda20a-a6fa-4214-8c7d-578f550b9ad7
Taylor, Richard D.
141004d4-95a6-44f1-93ce-ca36c1b34d61
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Michel, Julien, Taylor, Richard D. and Essex, Jonathan W.
(2004)
The parameterization and validation of generalized born models using the pairwise descreening approximation.
Journal of Computational Chemistry, 25 (14), .
(doi:10.1002/jcc.20105).
Abstract
Generalized Born Surface Area (GBSA) models for water using the Pairwise Descreening Approximation (PDA) have been parameterized by two different methods. The first method, similar to that used in previously reported parameterizations, optimizes all parameters against the experimental free energies of hydration of organic molecules. The second method optimizes the PDA parameters to compensate only for systematic errors of the PDA. The best models are compared to Poisson-Boltzmann calculations and applied to the computation of potentials of mean force (PMFs) for the association of various molecules. PMFs present a more rigorous test of the ability of a solvation model to correctly reproduce the screening of intermolecular interactions by the solvent, than its accuracy at predicting free energies of hydration of small molecules. Models derived with the first method are sometimes shown to fail to compute accurate potentials of mean force because of large errors in the computation of Born radii, while no such difficulties are observed with the second method. Furthermore, accurate computation of the Born radii appears to be more important than good agreement with experimental free energies of solvation. We discuss the source of errors in the potentials of mean force and suggest means to reduce them. Our findings suggest that Generalized Born models that use the Pairwise Descreening Approximation and that are derived solely by unconstrained optimization of parameters against free energies of hydration should be applied to the modeling of intermolecular interactions with caution.
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Published date: 15 November 2004
Keywords:
continuum solvation, generalized born, pairwise descreening
approximation, potentials of mean force, amino acid side chainacid side-chains, free-energy, mean force, atomic charges, computer-simulations, molecular mechanics, dielectric medium, solventmodels, nucleic-acids, solvation
Identifiers
Local EPrints ID: 20288
URI: http://eprints.soton.ac.uk/id/eprint/20288
ISSN: 1096-987X
PURE UUID: 8d9c3e88-e21f-4d74-9f8f-1abf20a76d75
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Date deposited: 20 Feb 2006
Last modified: 16 Mar 2024 02:45
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Author:
Julien Michel
Author:
Richard D. Taylor
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