CHARMM-GUI for Ligand Binding Site Prediction and Refinement.

A protein performs its task by binding a variety of ligands in its local region that is also known as the ligand-binding-site (LBS). Therefore, accurate prediction, characterization, and refinement of LBS can facilitate protein functional annotations and structure-based drug design. In this work, we present CHARMM-GUI (https://www.charmm-gui.org/input/lbsfinder) that predicts potential LBS, offers interactive features for local LBS structure analysis, and prepares various molecular dynamics (MD) systems and inputs by setting up distance restraint potentials for LBS structure refinement. supports 5 different commonly used simulation programs, such as NAMD, AMBER, GROMACS, GENESIS, and OpenMM, for LBS structure refinement together with hydrogen mass repartitioning. The capability of is illustrated through LBS structure predictions and refinements of 48 modeled and 20 apo benchmark target proteins. Overall, successful LBS structure predictions and refinements are seen in our benchmark tests. We hope that is useful to predict, characterize, and refine potential LBS on any given protein of interest.