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

, Maciej Blaszczyk

, Andrzej

Kolinski

, Sebastian Kmiecik

University of Warsaw, Warsaw, Poland,

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

. 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

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:

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.