Alchemical Enhanced Sampling with Optimized Phase Space Overlap.

ABSTRACT: An alchemical enhanced sampling (ACES) method has recently been introduced to facilitate importance sampling in free energy simulations. The method achieves enhanced sampling from Hamiltonian replica exchange within a dual topology framework while utilizing new smoothstep softcore potentials. A common sampling problem encountered in lead optimization is the functionalization of aromatic rings that exhibit distinct conformational preferences when interacting with the protein. It is difficult to converge the distribution of ring conformations due to the long time scale of ring flipping events; however, the ACES method addresses this issue by modeling the syn and anti ring conformations within a dual topology. ACES thereby samples the conformer distributions by alchemically tunn

SUBMITTER: Zhang S 

PROVIDER: S-EPMC11157682 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature