Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

15-POS Board 15 CABS-flex Web Server for Fast Simulations of Flexibility of Globular Proteins 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. Investigating of the conformational flexibility of protein structures is crucial for understanding their functions. Large timescales of protein molecular motions limit the applicability of standard molecular dynamics methods to this problem. Our method - CABS-flex 1,2 – implements a highly efficient, coarse-grained approach for prediction of fluctuations of the protein structures. The resulting structural ensembles reflect the flexibility of investigated protein and provide a picture complementary to the results obtained from molecular dynamics simulations 3 as well as NMR conformational ensembles 2 . The CABS-flex methodology is also successfully used for efficient simulations of protein flexibility in predictions of protein-peptide complexes 4,5 and protein aggregation properties 6 . The CABS-flex web server is freely available at: http://biocomp.chem.uw.edu.pl/CABSflex/. References: 1 Jamroz, M., Kolinski, A. & Kmiecik, S. CABS-flex: Server for fast simulation of protein structure fluctuations. Nucleic Acids Res 41, W427-431, doi:10.1093/nar/gkt332 (2013). 2 Jamroz, M., Kolinski, A. & Kmiecik, S. CABS-flex predictions of protein flexibility compared with NMR ensembles. Bioinformatics 30, 2150-2154, doi:10.1093/bioinformatics/btu184 (2014). 3 Jamroz, M., Orozco, M., Kolinski, A. & Kmiecik, S. Consistent View of Protein Fluctuations from All-Atom Molecular Dynamics and Coarse-Grained Dynamics with Knowledge-Based Force-Field. J Chem Theory Comput 9, 119-125, doi:10.1021/ct300854w (2013). 4 Ciemny, M. P. et al. Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction. Sci Rep 6, 37532, doi:10.1038/srep37532 (2016). 5 Ciemny, M., Kurcinski, M., Kozak, K., Koliński, A. & Kmiecik, S. in Methods in Molecular Biology Vol. 1561 69-94 (2017). 6 Zambrano, R. et al. AGGRESCAN3D (A3D): server for prediction of aggregation properties of protein structures. Nucleic Acids Res 43, W306-313, doi:10.1093/nar/gkv359 (2015).

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