Wright, DW;
Wan, S;
Meyer, C;
van Vlijmen, H;
Tresadern, G;
Coveney, PV;
(2019)
Application of ESMACS binding free energy protocols to diverse datasets: Bromodomain-containing protein 4.
Scientific Reports
, 9
(1)
, Article 6017. 10.1038/s41598-019-41758-1.
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Abstract
As the application of computational methods in drug discovery pipelines becomes more widespread it is increasingly important to understand how reproducible their results are and how sensitive they are to choices made in simulation setup and analysis. Here we use ensemble simulation protocols, termed ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent), to investigate the sensitivity of the popular molecular mechanics Poisson-Boltzmann surface area (MMPBSA) methodology. Using the bromodomain-containing protein 4 (BRD4) system bound to a diverse set of ligands as our target, we show that robust rankings can be produced only through combining ensemble sampling with multiple trajectories and enhanced solvation via an explicit ligand hydration shell.
| Type: | Article |
|---|---|
| Title: | Application of ESMACS binding free energy protocols to diverse datasets: Bromodomain-containing protein 4 |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-019-41758-1 |
| Publisher version: | https://doi.org/10.1038/s41598-019-41758-1 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10072650 |
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