Coarse-grained Protein Modeling: Dynamics, Folding Pathways and Mechanical Unfolding

From Computational Biophysics To Systems Biology Proceedings, 8, 83-90, 2012

Authors: Kolinski Andrzej, Błaszczyk Maciej, Kmiecik Sebastian


Coarse-grained protein modeling tool, CABS, is used in multiscale modeling of protein dynamics. It is demonstrated that the stochastic (Monte Carlo) dynamics, combined with all-atom refinement of the coarse-grained structures follows observed in experiments folding pathways of small proteins. The model is also used in model studies of chaperonin-assisted protein folding. It is shown that Iterative Annealing Mechanism of chaperonin action, where periodic distortion of the polypeptide chains by non-specific hydrophobic interactions can promote rapid folding and leads to a decrease in folding temperature. It is also demonstrated how chaperonin action prevents kinetically trapped conformations and modulates the observed folding mechanisms from nucleation-condensation to a more framework-like. Finally, the CABS model is used in simulations of mechanical unfolding, providing new ways for interpretation of Atomic Force Microscopy experiments.