New publication: how quickly can be calculate the effect of a mutation on an antibiotic? Philip Fowler, 20th November 202020th November 2020 The idea for this paper arose during talking over coffee at the BioExcel Alchemical Free Energy workshop in May 2019. We’d previously shown that alchemical free energy methods could successfully predict which mutations in S. aureus DHFR confer resistance to trimethoprim (and crucially, which do not). That is all well and good, but to do this at scale, we’d need to be able to run such calculations quickly, hence this paper. Part of the answer is making use of high performance computing, but part is also accepting that the primary goal of the calculations is not quantitative accuracy and precision, but instead resolving which side of a free threshold the change in antibiotic binding free energy induced by the mutation lies. That in turn enables the use of large numbers of very short lambda simulations which can be run in parallel, reducing the time-to-solution even further. This, or similar methods, could be used in drug development (to assess how many codon mutations could allow a protein to escape the action of an inhibitor) or in diagnostics. The paper is part of a special issue on Computational Medicine. Share this: Click to share on X (Opens in new window) X Click to share on Bluesky (Opens in new window) Bluesky Click to email a link to a friend (Opens in new window) Email Click to share on LinkedIn (Opens in new window) LinkedIn Click to share on Mastodon (Opens in new window) Mastodon Related antimicrobial resistance computing distributed computing GPUs molecular dynamics publication research
publication New Publication: State-Dependent Network Connectivity Determines Gating in a K+ Channel 27th June 2014 In an earlier paper we showed that the closed state of Kir1.1, a important potassium… Share this: Click to share on X (Opens in new window) X Click to share on Bluesky (Opens in new window) Bluesky Click to email a link to a friend (Opens in new window) Email Click to share on LinkedIn (Opens in new window) LinkedIn Click to share on Mastodon (Opens in new window) Mastodon Read More
GPAS stopover on the ORACLE road trip 1st February 20221st February 2022 You can listen to Philip Fowler talk about the Global Pathogen Analysis System (GPAS) as… Share this: Click to share on X (Opens in new window) X Click to share on Bluesky (Opens in new window) Bluesky Click to email a link to a friend (Opens in new window) Email Click to share on LinkedIn (Opens in new window) LinkedIn Click to share on Mastodon (Opens in new window) Mastodon Read More
antimicrobial resistance GPAS 17th May 202113th October 2021 I’ve been working on this for the last few months and very happy that we… Share this: Click to share on X (Opens in new window) X Click to share on Bluesky (Opens in new window) Bluesky Click to email a link to a friend (Opens in new window) Email Click to share on LinkedIn (Opens in new window) LinkedIn Click to share on Mastodon (Opens in new window) Mastodon Read More