How to Sample Dozens of Substitutions per Site with λ Dynamics.

ABSTRACT: Alchemical free energy methods are useful in computer-aided drug design and computational protein design because they provide rigorous statistical mechanics-based estimates of free energy differences from molecular dynamics simulations. λ dynamics is a free energy method with the ability to characterize combinatorial chemical spaces spanning thousands of related systems within a single simulation, which gives it a distinct advantage over other alchemical free energy methods that are mostly limited to pairwise comparisons. Recently developed methods have improved the scalability of λ dynamics to perturbations at many sites; however, the size of chemical space that can be explored at each individual site has previously been limited to fewer than ten substituents. As the number of substituent

SUBMITTER: Hayes RL 

PROVIDER: S-EPMC11270746 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature