Protein-Peptide Docking with High Conformational Flexibility using CABS-dock Web Tool

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 protein receptor surface, and then docking the peptide structure into the known binding site. This work (1) presents a comprehensive CABS-dock method (2) for the simultaneous search of binding sites and flexible protein–peptide docking. CABS-dock employs coarse-grained model CABS (3) - which unlike in structure-based models (4), retains both native and non-native interactions - efficient and versatile tool for modeling of proteins structure, dynamics and interactions (5-7). 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. The CABS-dock web server (2) is freely available at http://biocomp.chem.uw.edu.pl/CABSdock/.1. M. Blaszczyk et al., Methods, (Jul 10, 2015).2. M. Kurcinski, M. Jamroz, M. Blaszczyk, A. Kolinski, S. Kmiecik, Nucleic Acids Res43, W419 (Jul 1, 2015).3. A. Kolinski, Acta Biochim Pol51, 349 (2004).4. M. Kouza, C. K. Hu, M. S. Li, A. Kolinski, J Chem Phys139, (Aug 14, 2013).5. J. Wabik, S. Kmiecik, D. Gront, M. Kouza, A. Kolinski, Int J Mol Sci14, 9893 (May, 2013).6. S. Kmiecik, D. Gront, M. Kouza, A. Kolinski, J Phys Chem B116, 7026 (Jun 14, 2012).7. S. Kmiecik, M. Jamroz, M. Kolinski, Biophys J106, 2408 (Jun 3, 2014).