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Direct validation of the single step classical to quantum free energy perturbation

Direct validation of the single step classical to quantum free energy perturbation
Direct validation of the single step classical to quantum free energy perturbation
The use of the Zwanzig equation in the calculation of single-step perturbations to provide first-principles (ab initio) quantum mechanics (QM) correction terms to molecular mechanics (MM) free energy cycles is well established. A rigorous test of the ability to converge such calculations would be very useful in this context. In this work, we perform a direct assessment of the convergence of the MM to QM perturbation, by attempting the reverse QM to MM perturbation. This required the generation of extensive QM molecular dynamics trajectories, using density functional theory (DFT), within the representative biological system of a DNA adenosine–thymidine dimer. Over 100 ps of dynamics with the PBE functional and 6.25 ps with the LDA functional were generated. We demonstrate that calculations with total potential energies are very poorly convergent due to a lack of overlap of phase space distributions between ensembles. While not theoretically rigorous, the use of interaction energies provides far superior convergence, despite the presence of nonclassical charge transfer effects within the DFT trajectories. The source of poor phase space overlap for total energies is diagnosed, the approximate quantification of overlaps suggesting that even for the comparatively simple system considered here convergence of total energy calculations within a reasonable simulation time is unfeasible.
1520-6106
1017-1025
Cave-Ayland, Christopher
897f0885-28d7-4894-89f8-4b3cd100929b
Skylaris, Chris-Kriton
8f593d13-3ace-4558-ba08-04e48211af61
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Cave-Ayland, Christopher
897f0885-28d7-4894-89f8-4b3cd100929b
Skylaris, Chris-Kriton
8f593d13-3ace-4558-ba08-04e48211af61
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5

Cave-Ayland, Christopher, Skylaris, Chris-Kriton and Essex, Jonathan W. (2015) Direct validation of the single step classical to quantum free energy perturbation. [in special issue: William L. Jorgensen Festschrift] The Journal of Physical Chemistry B, 119 (3), 1017-1025. (doi:10.1021/jp506459v).

Record type: Article

Abstract

The use of the Zwanzig equation in the calculation of single-step perturbations to provide first-principles (ab initio) quantum mechanics (QM) correction terms to molecular mechanics (MM) free energy cycles is well established. A rigorous test of the ability to converge such calculations would be very useful in this context. In this work, we perform a direct assessment of the convergence of the MM to QM perturbation, by attempting the reverse QM to MM perturbation. This required the generation of extensive QM molecular dynamics trajectories, using density functional theory (DFT), within the representative biological system of a DNA adenosine–thymidine dimer. Over 100 ps of dynamics with the PBE functional and 6.25 ps with the LDA functional were generated. We demonstrate that calculations with total potential energies are very poorly convergent due to a lack of overlap of phase space distributions between ensembles. While not theoretically rigorous, the use of interaction energies provides far superior convergence, despite the presence of nonclassical charge transfer effects within the DFT trajectories. The source of poor phase space overlap for total energies is diagnosed, the approximate quantification of overlaps suggesting that even for the comparatively simple system considered here convergence of total energy calculations within a reasonable simulation time is unfeasible.

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e-pub ahead of print date: 19 September 2014
Published date: 22 January 2015
Organisations: Computational Systems Chemistry

Identifiers

Local EPrints ID: 390566
URI: https://eprints.soton.ac.uk/id/eprint/390566
ISSN: 1520-6106
PURE UUID: 6a835ba0-5289-4292-b1ec-5865309f2ca4
ORCID for Chris-Kriton Skylaris: ORCID iD orcid.org/0000-0003-0258-3433
ORCID for Jonathan W. Essex: ORCID iD orcid.org/0000-0003-2639-2746

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Date deposited: 05 Apr 2016 08:01
Last modified: 19 Jul 2019 01:16

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