Impact of Varying Velocities and Solvation Boxes on Alchemical Free-Energy Simulations.

ABSTRACT: Alchemical free-energy perturbation (FEP) is an accurate and thermodynamically stringent way to estimate relative energies for the binding of small ligands to biological macromolecules. It has repeatedly been pointed out that a single simulation normally stays near the starting point in phase space and therefore underestimates the uncertainty of the results. Therefore, it is better to run an ensemble of independent simulations. Traditionally, such an ensemble has been generated by using different starting velocities. We argue that it is better to use also other random choices made during the setup of the simulations, in particular the solvation of the solute. We show here that such solvent-induced independent simulations (SIS) sometimes give a larger standard deviation and slightly differe

SUBMITTER: Wang M 

PROVIDER: S-EPMC11863368 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature