Multi-Pole Approach to Structural Science

May 10 - 13, 2015

Towards unrestrained protein-protein molecular docking
Andrzej Kolinski

Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw

Pasteura 1, 02-093 Warsaw, Poland


Laboratory of Theory of Biopolymers develops novel molecular modeling methods which enable efficient simulations of flexible protein docking. The new methods are expected to qualitatively surpass the currently available docking protocols by including the full structural mobility of smaller molecules forming a complex (peptides and small proteins) and the substantial conformational flexibility of proteins (or protein complexes) that bind with them. No information about the approximate location of the binding site(s) will be required. The modeling procedures are not limited only to the structure prediction of protein complexes, but are also applicable to the investigation of the mechanisms of complex formation and characterization of their dynamic properties (1). Multiscale modeling schemes start from coarse-grained representation and continue on more detailed models, finally refining the results on all-atom level. Preliminary results show that the methods provide realistic pictures of protein-protein docking of small molecules (2) and enable fast and dependable structure prediction of protein-peptide complexes (3). Development of multiscale modeling tools for structure predictions of larger protein complexes is now in progress.

(1) M. Jamroz, M. Orozco, A. Kolinski & S. Kmiecik, “A Consistent View of Protein Fluctuations from All-atom Molecular Dynamics and Coarse-Grained Dynamics with Knowledge-based Force-field”, J. Chem, Theo. Comp. 9:119-125 (2013)

(2) M. Kurcinski, A. Kolinski & S. Kmiecik, “Mechanism of folding and binding of an intrinsically disordered protein as revealed by ab initio simulations”, J. Chem. Theo. Comp. 10(6):2224-2231 (2014)

(3) M. Kurcinski, M. Jamroz, M. Blaszczyk, A. Kolinski & S. Kmiecik, “CABS-dock: server for flexible peptide-protein docking”, Nucleic Acids Research, submitted