Wu, Q;
Huang, T;
Xia, S;
Otto, F;
Lee, TY;
Huang, HD;
Chiang, YC;
(2022)
On the force field optimisation of β -lactam cores using the force field Toolkit.
Journal of Computer-Aided Molecular Design
10.1007/s10822-022-00464-3.
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Abstract
When employing molecular dynamics (MD) simulations for computer-aided drug design, the quality of the used force fields is highly important. Here we present reparametrisations of the force fields for the core molecules from 9 different β-lactam classes, for which we utilized the force field Toolkit and Gaussian calculations. We focus on the parametrisation of the dihedral angles, with the goal of reproducing the optimised quantum geometry in MD simulations. Parameters taken from CGenFF turn out to be a good initial guess for the multiplicity of each dihedral angle, but the key to a successful parametrisation is found to lie in the phase shifts. Based on the optimised quantum geometry, we come up with a strategy for predicting the phase shifts prior to the dihedral potential fitting. This allows us to successfully parameterise 8 out of the 11 molecules studied here, while the remaining 3 molecules can also be parameterised with small adjustments. Our work highlights the importance of predicting the dihedral phase shifts in the ligand parametrisation protocol, and provides a simple yet valuable strategy for improving the process of parameterising force fields of drug-like molecules.
| Type: | Article |
|---|---|
| Title: | On the force field optimisation of β -lactam cores using the force field Toolkit |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s10822-022-00464-3 |
| Publisher version: | https://doi.org/10.1007/s10822-022-00464-3 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | CGenFF, Dihedral phase shifts prediction, Ligand force field parametrisation, ffTK |
| UCL classification: | UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10153718 |
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