Preventing lipophilic aggregation in cosolvent molecular dynamics simulations with hydrophobic probes using Plumed Automatic Restraining Tool (PART).

ABSTRACT: Cosolvent molecular dynamics (MD) simulations are molecular dynamics simulations used to identify preferable locations of small organic fragments on a protein target. Most cosolvent molecular dynamics workflows make use of only water-soluble fragments, as hydrophobic fragments would cause lipophilic aggregation. To date the two approaches that allow usage of hydrophobic cosolvent molecules are to use a low (0.2 M) concentration of hydrophobic probes, with the disadvantage of a lower sampling speed, or to use force field modifications, with the disadvantage of a difficult and inflexible setup procedure. Here we present a third alternative, that does not suffer from low sampling speed nor from cumbersome preparation procedures. We have built an easy-to-use open source command line tool PART

SUBMITTER: Beyens O 

PROVIDER: S-EPMC10898161 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature