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On the issues impacting reproducibility of alchemical free energy calculations

On the issues impacting reproducibility of alchemical free energy calculations
On the issues impacting reproducibility of alchemical free energy calculations

Whilst the quality of force fields and sampling methodologies has improved significantly over the years, along with the accessible lengths of simulations, there still remain a number of factors which limit the reproducibility of relative binding free energy calculations. In this chapter, we discuss a number of the choices affecting the ability of independent research teams to obtain statistically equivalent results for a given free energy calculation, and also those factors which affect the precision of a given set of calculations. We also discuss some of the published methods which are able to resolve or minimize these issues, and suggest future directions as to how researchers can maximize the reproducibility of their work.

0097-6156
109-125
American Chemical Society
Suruzhon, Miroslav
4ea4dd8b-0a98-4598-9eaa-756d943b5dca
Samways, Marley L.
75cda5aa-31ef-4f62-9ea3-8655ea55d3fb
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Armacost, Kira A.
Thompson, David C.
Suruzhon, Miroslav
4ea4dd8b-0a98-4598-9eaa-756d943b5dca
Samways, Marley L.
75cda5aa-31ef-4f62-9ea3-8655ea55d3fb
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Armacost, Kira A.
Thompson, David C.

Suruzhon, Miroslav, Samways, Marley L. and Essex, Jonathan W. (2021) On the issues impacting reproducibility of alchemical free energy calculations. In, Armacost, Kira A. and Thompson, David C. (eds.) Free Energy Methods in Drug Discovery: Current State and Future Directions. (ACS Symposium Series, 1397) American Chemical Society, pp. 109-125. (doi:10.1021/bk-2021-1397.ch004).

Record type: Book Section

Abstract

Whilst the quality of force fields and sampling methodologies has improved significantly over the years, along with the accessible lengths of simulations, there still remain a number of factors which limit the reproducibility of relative binding free energy calculations. In this chapter, we discuss a number of the choices affecting the ability of independent research teams to obtain statistically equivalent results for a given free energy calculation, and also those factors which affect the precision of a given set of calculations. We also discuss some of the published methods which are able to resolve or minimize these issues, and suggest future directions as to how researchers can maximize the reproducibility of their work.

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Published date: 19 November 2021
Additional Information: Publisher Copyright: © 2021 American Chemical Society. All rights reserved.

Identifiers

Local EPrints ID: 472528
URI: http://eprints.soton.ac.uk/id/eprint/472528
ISSN: 0097-6156
PURE UUID: 045cfaf5-b01d-4053-a11b-0ee6898bee25
ORCID for Marley L. Samways: ORCID iD orcid.org/0000-0001-9431-8789
ORCID for Jonathan W. Essex: ORCID iD orcid.org/0000-0003-2639-2746

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Date deposited: 07 Dec 2022 17:52
Last modified: 06 Jun 2024 01:34

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Contributors

Author: Miroslav Suruzhon
Author: Marley L. Samways ORCID iD
Editor: Kira A. Armacost
Editor: David C. Thompson

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