Colabind: A Cloud-Based Approach for Prediction of Binding Sites Using Coarse-Grained Simulations with Molecular Probes

J Phys Chem B. 2024 Apr 4;128(13):3211-3219. doi: 10.1021/acs.jpcb.3c07853. Epub 2024 Mar 21.

Abstract

Binding site prediction is a crucial step in understanding protein-ligand and protein-protein interactions (PPIs) with broad implications in drug discovery and bioinformatics. This study introduces Colabind, a robust, versatile, and user-friendly cloud-based approach that employs coarse-grained molecular dynamics simulations in the presence of molecular probes, mimicking fragments of drug-like compounds. Our method has demonstrated high effectiveness when validated across a diverse range of biological targets spanning various protein classes, successfully identifying orthosteric binding sites, as well as known druggable allosteric or PPI sites, in both experimentally determined and AI-predicted protein structures, consistently placing them among the top-ranked sites. Furthermore, we suggest that careful inspection of the identified regions with a high affinity for specific probes can provide valuable insights for the development of pharmacophore hypotheses. The approach is available at https://github.com/porekhov/CG_probeMD.

MeSH terms

  • Binding Sites
  • Cloud Computing*
  • Ligands
  • Molecular Dynamics Simulation
  • Molecular Probes*
  • Protein Binding
  • Proteins / chemistry

Substances

  • Molecular Probes
  • Proteins
  • Ligands