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 N. Falcone
Stephen D. Pickett
Dr David Rogers DAVID.ROGERS@NOTTINGHAM.AC.UK
SENIOR 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. (2023). Free energy perturbation calculations of tetrahydroquinolines complexed to the first bromodomain of BRD4. Molecular Physics, 121(9-10), Article e2124201. 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 | 2023 |
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 |
Volume | 121 |
Issue | 9-10 |
Article Number | e2124201 |
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
(2.6 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
You might also like
An Improved Diabatization Scheme for Computing the Electronic Circular Dichroism of Proteins
(2024)
Journal Article
Artificial intelligence for small molecule anticancer drug discovery
(2024)
Journal Article
Solvent flashcards: a visualisation tool for sustainable chemistry.
(2024)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2025
Advanced Search