Arnaldo F. Silva
Free energy perturbation calculations of tetrahydroquinolines complexed to the first bromodomain of BRD4
Silva, Arnaldo F.; Guest, Ellen E.; Falcone, Bruno N.; Pickett, Stephen D.; Rogers, David M.; Hirst, Jonathan D.
Authors
Ellen E. Guest
BRUNO FALCONE PIN Bruno.FalconePin@nottingham.ac.uk
Research Fellow
Stephen D. Pickett
DOCTOR DAVID ROGERS DAVID.ROGERS@NOTTINGHAM.AC.UK
Research Fellow
Professor JONATHAN HIRST JONATHAN.HIRST@NOTTINGHAM.AC.UK
Professor of Computational Chemistry
Abstract
Alchemical free energy perturbation (FEP) theory is widely used nowadays to calculate protein–ligand binding energies, often in support of drug discovery endeavours. We assess the accuracy and sensitivity of absolute FEP binding energies with respect to the CHARMM/CGenFF and the AMBER/GAFF force field parameterisations for a set of tetrahydroquinoline inhibitors of the first bromodomain of BRD4, a target of keen interest for the development of anti-cancer drugs. We find that AMBER/GAFF is better able than CHARMM/CGenFF to cover the range of and to distinguish between the relative binding energies of the 16 ligands.
Citation
Silva, A. F., Guest, E. E., Falcone, B. N., Pickett, S. D., Rogers, D. M., & Hirst, J. D. (2022). Free energy perturbation calculations of tetrahydroquinolines complexed to the first bromodomain of BRD4. Molecular Physics, https://doi.org/10.1080/00268976.2022.2124201
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 6, 2022 |
Online Publication Date | Oct 12, 2022 |
Publication Date | Oct 12, 2022 |
Deposit Date | Sep 26, 2022 |
Publicly Available Date | Oct 13, 2023 |
Journal | Molecular Physics |
Print ISSN | 0026-8976 |
Electronic ISSN | 1362-3028 |
Publisher | Taylor and Francis |
Peer Reviewed | Peer Reviewed |
DOI | https://doi.org/10.1080/00268976.2022.2124201 |
Keywords | Physical and Theoretical Chemistry; Condensed Matter Physics; Molecular Biology; Biophysics |
Public URL | https://nottingham-repository.worktribe.com/output/11744230 |
Publisher URL | https://www.tandfonline.com/doi/full/10.1080/00268976.2022.2124201 |
Files
Jonathan Hirst Free Energy Perturbation
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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