eprintid: 10192066 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/19/20/66 datestamp: 2024-05-09 15:59:33 lastmod: 2024-05-09 15:59:33 status_changed: 2024-05-09 15:59:33 type: article metadata_visibility: show sword_depositor: 699 creators_name: Edeling, Wouter creators_name: Vassaux, Maxime creators_name: Yang, Yiming creators_name: Wan, Shunzhou creators_name: Guillas, Serge creators_name: Coveney, Peter V title: Global ranking of the sensitivity of interaction potential contributions within classical molecular dynamics force fields ispublished: pub divisions: UCL divisions: B04 divisions: C06 divisions: F56 note: 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/. abstract: Uncertainty quantification (UQ) is rapidly becoming a sine qua non for all forms of computational science out of which actionable outcomes are anticipated. Much of the microscopic world of atoms and molecules has remained immune to these developments but due to the fundamental problems of reproducibility and reliability, it is essential that practitioners pay attention to the issues concerned. Here a UQ study is undertaken of classical molecular dynamics with a particular focus on uncertainties in the high-dimensional force-field parameters, which affect key quantities of interest, including material properties and binding free energy predictions in drug discovery and personalized medicine. Using scalable UQ methods based on active subspaces that invoke machine learning and Gaussian processes, the sensitivity of the input parameters is ranked. Our analyses reveal that the prediction uncertainty is dominated by a small number of the hundreds of interaction potential parameters within the force fields employed. This ranking highlights what forms of interaction control the prediction uncertainty and enables systematic improvements to be made in future optimizations of such parameters. date: 2024-05-03 date_type: published publisher: Springer Science and Business Media LLC official_url: https://doi.org/10.1038/s41524-024-01272-z oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2273517 doi: 10.1038/s41524-024-01272-z lyricists_name: Wan, Shunzhou lyricists_name: Coveney, Peter lyricists_id: SWANX17 lyricists_id: PCOVE58 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: npj Computational Materials volume: 10 article_number: 87 issn: 2057-3960 citation: Edeling, Wouter; Vassaux, Maxime; Yang, Yiming; Wan, Shunzhou; Guillas, Serge; Coveney, Peter V; (2024) Global ranking of the sensitivity of interaction potential contributions within classical molecular dynamics force fields. npj Computational Materials , 10 , Article 87. 10.1038/s41524-024-01272-z <https://doi.org/10.1038/s41524-024-01272-z>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10192066/1/s41524-024-01272-z.pdf