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

J Chem Inf Model. 2021 Nov 22;61(11):5336-5342. doi: 10.1021/acs.jcim.1c01156. Epub 2021 Nov 10.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Ligands
  • Molecular Dynamics Simulation*
  • Protein Binding
  • Proteins* / metabolism

Substances

  • Ligands
  • Proteins