A Method for Treating Significant Conformational Changes in Alchemical Free Energy Simulations of Protein-Ligand Binding.

ABSTRACT: Relative binding free energy (RBFE) simulation is a rigorous approach to the calculation of quantitatively accurate binding free energy values for protein-ligand binding in which a reference binder is gradually converted to a target binder through alchemical transformation during the simulation. The success of such simulations relies on being able to accurately sample the correct conformational phase space for each alchemical state; however, this becomes a challenge when a significant conformation change occurs between the reference and target binder-receptor complexes. Increasing the simulation time and using enhanced sampling methods can be helpful, but effects can be limited, especially when the free energy barrier between conformations is high or when the correct target complex conform

SUBMITTER: Liao J 

PROVIDER: S-EPMC11513859 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature