Automated On-the-Fly Optimization of Resource Allocation for Efficient Free Energy Simulations.

ABSTRACT: Computing the free energy of protein-ligand binding by employing molecular dynamics (MD) simulations is becoming a valuable tool in the early stages of drug discovery. However, the cost and complexity of such simulations are often prohibitive for high-throughput studies. We present an automated workflow for the thermodynamic integration scheme with the "on-the-fly" optimization of computational resource allocation for each λ-window of both relative and absolute binding free energy simulations. This iterative workflow utilizes automatic equilibration detection and convergence testing via the Jensen-Shannon distance to determine optimal simulation stopping points in an entirely data-driven manner. It is broadly applicable to multiple free energy calculations, such as ligand binding, amino ac

SUBMITTER: Koby SB 

PROVIDER: S-EPMC12121625 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature