Modeling of protein-peptide interactions using the CABS-dock web server for binding site search and flexible docking

TL;DR

This paper introduces CABS-dock, a web server that simultaneously predicts protein-peptide binding sites and performs flexible docking, streamlining the modeling process with user-friendly tools and advanced options.

Contribution

It presents a comprehensive, user-friendly web server for simultaneous binding site prediction and flexible docking, with strategies to enhance accuracy using molecular dynamics.

Findings

Successful demonstration of CABS-dock on various examples

Enhanced flexibility options improve docking accuracy

Assessment with molecular dynamics boosts model quality

Abstract

Protein-peptide interactions play essential functional roles in living organisms and their structural characterization is a hot subject of current experimental and theoretical research. Computational modeling of the structure of protein-peptide interactions is usually divided into two stages: prediction of the binding site at a protein receptor surface, and then docking (and modeling) the peptide structure into the known binding site. This paper presents a comprehensive CABS-dock method for the simultaneous search of binding sites and flexible protein-peptide docking, available as a users friendly web server. We present example CABS-dock results obtained in the default CABS-dock mode and using its advanced options that enable the user to increase the range of flexibility for chosen receptor fragments or to exclude user-selected binding modes from docking search. Furthermore, we demonstrate a strategy to improve CABS-dock performance by assessing the quality of models with classical molecular dynamics. Finally, we discuss the promising extensions and applications of the CABS-dock method and provide a tutorial appendix for the convenient analysis and visualization of CABS-dock results. The CABS-dock web server is freely available at http://biocomp.chem.uw.edu.pl/CABSdock/