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

• Published in: Methods (San Diego, Calif.) Vol. 93; pp. 72 - 83
• Main Authors: Blaszczyk, Maciej, Kurcinski, Mateusz, Kouza, Maksim, Wieteska, Lukasz, Debinski, Aleksander, Kolinski, Andrzej, Kmiecik, Sebastian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.01.2016
• Subjects: binding sites; Binding Sites - physiology; CABS-dock; Flexible docking; Internet; Models, Molecular; Molecular docking; Molecular Docking Simulation - methods; molecular dynamics; Peptide binding; Peptide folding; Peptides - chemistry; Peptides - metabolism; prediction; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins - chemistry; Proteins - metabolism; Protein–peptide docking; Web Browser; Protein–peptide docking; Peptide binding; Flexible docking; CABS-dock; Molecular docking; Peptide folding
• ISSN: 1046-2023; 1095-9130; 1095-9130
• DOI: 10.1016/j.ymeth.2015.07.004

[Display omitted] •CABS-dock method for protein–peptide molecular docking is presented.•CABS-dock performs docking of fully flexible peptides to flexible proteins.•CABS-dock doesn’t require knowledge about the peptide binding site.•Tutorial for visualization and analysis of CABS-dock results is provided. 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 user’s 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/.