A simple coarse-grained model forself-assembling silk-like protein fibers

摘要

Collagen-silk-collagen triblock polypeptides can self-assemble at low pH intonanometer thin fibers with a length in the order of micrometers. Previously wepredicted, via all-atom simulations, the structure of the folded silk domain to bea 13-roll. In this work we develop a simple coarse-grained model of the silkdomain to enable a numerical study of the fiber's properties and formation ona larger length and time scale. As an initial coarse-grained model for thefiber forming protein we chose the model of Brown et al., Proc. Natl. Acad. Sci.U. S. A., 2003, 100, 10712-10717. We adapted this model, and optimized itsparameters to reproduce the all-atom molecular dynamics simulation structuraldata. The unknown strength of the attraction between the beads representing theresidues is optimized by computing the Potential of Mean Force for unfoldinga strand of the (3-roll, using non-equilibrium steered MD simulations incombination with the Jarzynski relation. Using these optimized parameters weobserved spontaneous folding of a short peptide. The coarse-grained (3-roll, aswell as a much larger stack (a fiber) of 13-rolls, were found to be stable. Moreover,the predicted fiber persistence length is in agreement with experiment. Theefficacy of the mapping of a coarse-grained system onto an all-atom simulation isdiscussed. The approach opens the way for large-scale simulations of fibers,based on molecular structure, and allows investigation of their nucleation,growth, cross-linking mechanism, network dynamics, and rheology.