Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

14-POS Board 14 CABS-dock Web Server for Protein-Peptide Docking with Large-scale Flexibility of a Protein Receptor Maciej Ciemny 2,1 , Karolina Dawid 2,1 , Mateusz Kurcinski 1 , Maciej Blaszczyk 1 , Andrzej Kolinski 1 , Sebastian Kmiecik 1 . 1 University of Warsaw, Warsaw, Poland, 2 University of Warsaw, Warsaw, Poland. Protein-peptide interactions may involve large-scale conformational changes of a protein receptor, that are challenging to study either by experiment or computationally 1 . Here, we present our method for flexible protein-peptide docking – the CABS-dock 2-4 . The method performs a blind global search for a binding site combined with an on-the-fly folding of a fully flexible peptide, while the receptor backbone fluctuates around its input conformation. In CABS- dock, the flexibility of chosen protein regions may be assigned as fully flexible by a user to allow for large-scale conformational changes. This method was applied to modeling of the MDM2/p53 complex, in which the receptor contains intrinsically disordered regions of significant length 1 . The obtained results matched well the experimental data and provided new insights into the possible role of unstructured receptor regions. CABS-dock is available as a web server at: http://biocomp.chem.uw.edu.pl/CABSdock. References: 1. Ciemny, M. P.; Debinski, A.; Paczkowska, M.; Kolinski, A.; Kurcinski, M.; Kmiecik, S., Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction. Sci Rep 2016, 6, 37532. 2. Ciemny, M.; Kurcinski, M.; Kozak, K.; Koliński, A.; Kmiecik, S. Highly flexible protein- peptide docking using CABS-dock. In Methods in Molecular Biology; 2017; Vol. 1561, pp 69- 94. 3. Blaszczyk, M.; Kurcinski, M.; Kouza, M.; Wieteska, L.; Debinski, A.; Kolinski, A.; Kmiecik, S., Modeling of protein-peptide interactions using the CABS-dock web server for binding site search and flexible docking. Methods 2016, 93, 72-83. 4. Kurcinski, M.; Jamroz, M.; Blaszczyk, M.; Kolinski, A.; Kmiecik, S., CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site. Nucleic Acids Res 2015, 43, W419-24.

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