CHARMM-GUI for Template-Based Virtual Ligand Design in a Binding Site.

Rational drug design involves a task of finding ligands that would bind to a specific target protein. This work presents CHARMM-GUI that is an intuitive and interactive web-based tool to design virtual ligands that match the shape and chemical features of a given protein binding site. provides ligand modification capabilities with 3D visualization that allow researchers to modify and redesign virtual ligands while viewing how the protein-ligand interactions are affected. Virtual ligands can also be parameterized for further molecular dynamics (MD) simulations and free energy calculations. Using 8 targets from 8 different protein classes in the directory of useful decoys, enhanced (DUD-E) data set, we show that can produce similar ligands to the known active ligands in the crystal structures. also produces stable protein-ligand complex structures when tested using short MD simulations. We expect that can be a useful and user-friendly tool to design small molecules in any given potential ligand binding site on a protein of interest.