CHARMM-GUI <i>Ligand Designer</i> for Template-Based Virtual Ligand Design in a Binding Site
Hugo Guterres, Sang‐Jun Park, Yiwei Cao, Wonpil Im
Abstract
Rational drug design involves a task of finding ligands that would bind to a specific target protein. This work presents CHARMM-GUI Ligand Designer 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. Ligand Designer 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 Ligand Designer can produce similar ligands to the known active ligands in the crystal structures. Ligand Designer also produces stable protein–ligand complex structures when tested using short MD simulations. We expect that Ligand Designer can be a useful and user-friendly tool to design small molecules in any given potential ligand binding site on a protein of interest.