Bulletin of the American Physical Society
APS March Meeting 2022
Volume 67, Number 3
Monday–Friday, March 14–18, 2022; Chicago
Session K06: Physics of Proteins III: Evolution and Function of Molecular Interactions
3:00 PM–5:48 PM,
Tuesday, March 15, 2022
Room: McCormick Place W-178B
Sponsoring Unit: DBIO
Chair: Tatjana Skrbic, University of Oregon
Abstract: K06.00007 : Comparison of α-conotoxin free energy landscapes via simulation and dimensionality reduction*
5:00 PM–5:12 PM
Ré A Mansbach
Conotoxins are short, disulfide-rich peptides of interest as therapeutic candidates. Because of the combinatorial nature of the way their cysteines can covalently connect, they can exist in metastable ensembles of structurally distinct "disulfide isomers," which makes them particularly difficult to explore in silico. Traditional molecular dynamics cannot capture the breaking and reforging of disulfide bonds. Here, we simulate four α-conotoxins, containing four cysteines, with their disulfide bonds unconnected. We construct different low-dimensional models to compare their free energies and explore how we can transform between them with minimal additional simulation time. This work represents a first step in the creation of a unified search space for disulfide-rich peptides as therapeutic candidates.
*This work was supported by NSERC grant #RGPIN-2021-03470. This research was undertaken, in part, thanks to funding from the Canada Research Chairs Program.
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