Proteins exist in solution as ensembles of structurally different conformations. These ensembles can exhibit different degrees of structural diversity, ranging from almost static to highly heterogeneous. Structural flexibility allows proteins to play important functions in living cells. Therefore, characterization of protein structural changes can provide important insights into cell mechanisms and new therapies.

Recently, we developed an efficient modeling method for the characterization of flexibility of globular proteins. The method have been made available as CABS-flex (http://biocomp.chem.uw.edu.pl/CABSflex) server [1]. The CABS-flex was shown to be a computationally efficient alternative to all-atom molecular dynamics - a classical simulation approach [2]. Moreover, we demonstrated that the relative fluctuations of protein residues obtained from CABS-flex are well correlated to those of NMR ensembles [3]. Based on a similar modeling approach, we have also developed a method for the modeling of highly dynamic protein complexes. This method allowed us to characterize the mechanism of coupled folding and binding of an intrinsically disordered protein [4]. The obtained ensemble of highly heterogeneous complexes agreed well with experimental data.

References:

[1] Jamroz M, Kolinski A, Kmiecik S. CABS-flex: server for fast simulation of protein structure fluctuations. Nucleic Acids Research, 41:W427-W431, 2013

[2] 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. Journal of Chemical Theory and Computation, 9:119 - 125, 2013

[3] Jamroz M, Kolinski A, Kmiecik S. CABS-flex predictions of protein flexibility compared with NMR ensembles. Bioinformatics, in press, 2014

[4] Kurcinski M, Kolinski A, Kmiecik S. Mechanism of Folding and Binding of an Intrinsically Disordered Protein as Revealed by Ab Initio Simulations. (submitted)

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