<scp>CHARMM‐GUI</scp><i>high‐throughput simulator</i> for efficient evaluation of protein–ligand interactions with different force fields

Abstract Molecular docking is one of the most popular computational tools for hit discovery step in drug design. However, there ample room improvement docking's ability to identify correct binding modes and discriminate active from decoy compounds. dynamics (MD) simulations protein–ligand structures have been shown be effective improving results. Here, we present CHARMM‐GUI high‐throughput simulator (HTS) that prepares MD simulation systems inputs multiple complex a manner. HTS supports commonly used programs (NAMD, GROMACS, AMBER, OpenMM, GENESIS, Desmond, LAMMPS, Tinker) along with various force field combinations protein ligand, including CHARMM36m, Amber (ff19SB/ff14SB), OPLS‐AA/M, CGenFF, GAFF2, OpenFF. Validation tests using Miller directory useful decoys‐enhanced (DUD‐E) datasets demonstrate short HTS‐generated simple ligand RMSD calculations consistently outperform Specifically, can better ligand‐binding among top 10 poses as compared scores. In addition, compounds DUD‐E dataset than scores both soluble membrane proteins. We expect tool facilitate process design by