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Large-scale binding affinity calculations on commodity compute clouds
In recent years, it has become possible to calculate binding affinities of compounds bound to proteins via rapid, accurate, precise and reproducible free energy calculations. This is imperative in drug discovery as well as personalized medicine. This approach is based on molecular dynamics (MD) simu...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653340/ https://www.ncbi.nlm.nih.gov/pubmed/33178415 http://dx.doi.org/10.1098/rsfs.2019.0133 |
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author | Zasada, S. J. Wright, D. W. Coveney, P. V. |
author_facet | Zasada, S. J. Wright, D. W. Coveney, P. V. |
author_sort | Zasada, S. J. |
collection | PubMed |
description | In recent years, it has become possible to calculate binding affinities of compounds bound to proteins via rapid, accurate, precise and reproducible free energy calculations. This is imperative in drug discovery as well as personalized medicine. This approach is based on molecular dynamics (MD) simulations and draws on sequence and structural information of the protein and compound concerned. Free energies are determined by ensemble averages of many MD replicas, each of which requires hundreds of cores and/or GPU accelerators, which are now available on commodity cloud computing platforms; there are also requirements for initial model building and subsequent data analysis stages. To automate the process, we have developed a workflow known as the binding affinity calculator. In this paper, we focus on the software infrastructure and interfaces that we have developed to automate the overall workflow and execute it on commodity cloud platforms, in order to reliably predict their binding affinities on time scales relevant to the domains of application, and illustrate its application to two free energy methods. |
format | Online Article Text |
id | pubmed-7653340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-76533402020-11-10 Large-scale binding affinity calculations on commodity compute clouds Zasada, S. J. Wright, D. W. Coveney, P. V. Interface Focus Articles In recent years, it has become possible to calculate binding affinities of compounds bound to proteins via rapid, accurate, precise and reproducible free energy calculations. This is imperative in drug discovery as well as personalized medicine. This approach is based on molecular dynamics (MD) simulations and draws on sequence and structural information of the protein and compound concerned. Free energies are determined by ensemble averages of many MD replicas, each of which requires hundreds of cores and/or GPU accelerators, which are now available on commodity cloud computing platforms; there are also requirements for initial model building and subsequent data analysis stages. To automate the process, we have developed a workflow known as the binding affinity calculator. In this paper, we focus on the software infrastructure and interfaces that we have developed to automate the overall workflow and execute it on commodity cloud platforms, in order to reliably predict their binding affinities on time scales relevant to the domains of application, and illustrate its application to two free energy methods. The Royal Society 2020-12-06 2020-10-16 /pmc/articles/PMC7653340/ /pubmed/33178415 http://dx.doi.org/10.1098/rsfs.2019.0133 Text en © 2020 The Authors. http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Articles Zasada, S. J. Wright, D. W. Coveney, P. V. Large-scale binding affinity calculations on commodity compute clouds |
title | Large-scale binding affinity calculations on commodity compute clouds |
title_full | Large-scale binding affinity calculations on commodity compute clouds |
title_fullStr | Large-scale binding affinity calculations on commodity compute clouds |
title_full_unstemmed | Large-scale binding affinity calculations on commodity compute clouds |
title_short | Large-scale binding affinity calculations on commodity compute clouds |
title_sort | large-scale binding affinity calculations on commodity compute clouds |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653340/ https://www.ncbi.nlm.nih.gov/pubmed/33178415 http://dx.doi.org/10.1098/rsfs.2019.0133 |
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