A simple coarse-grained model for self-assembling silk-like protein fibers.
A simple coarse-grained model for self-assembling silk-like protein fibers.
复制标题
用于自组装丝状蛋白纤维的简单粗粒模型。
作者：
M. Schor;B. Ensing;P. Bolhuis
胶原-丝-胶原三嵌段多肽可以在低pH下自组装成长度为微米量级的纳米细纤维。之前我们通过全原子模拟预测，折叠的丝结构域的结构是β-卷。在这项工作中，我们开发了一个简单的粗粒度模型的丝域，使数值研究的纤维的性质和形成在一个更大的长度和时间尺度。作为纤维形成蛋白的初始粗粒模型，我们选择Brown等人的模型，Proc. Natl.美国科学院美国，2003，100，10712-10717。我们调整了该模型，并优化了其参数，以重现全原子分子动力学模拟的结构数据。代表残基的珠子之间的吸引力的未知强度通过使用非平衡转向MD模拟结合Jarzynski关系计算用于展开β-卷的链的平均力的势来优化。使用这些优化的参数，我们观察到自发折叠的短肽。发现粗颗粒β-辊以及β-辊的大得多的堆叠（纤维）是稳定的。此外，预测的光纤持久长度与实验相一致。一个粗粒度的系统映射到一个全原子模拟的功效进行了讨论。该方法为基于分子结构的大规模纤维模拟开辟了道路，并允许对其成核，生长，交联机制，网络动力学和流变学进行研究。
Collagen-silk-collagen triblock polypeptides can self-assemble at low pH into nanometer thin fibers with a length in the order of micrometers. Previously we predicted, via all-atom simulations, the structure of the folded silk domain to be a beta-roll. In this work we develop a simple coarse-grained model of the silk domain to enable a numerical study of the fiber's properties and formation on a larger length and time scale. As an initial coarse-grained model for the fiber 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 its parameters to reproduce the all-atom molecular dynamics simulation structural data. The unknown strength of the attraction between the beads representing the residues is optimized by computing the Potential of Mean Force for unfolding a strand of the beta-roll, using non-equilibrium steered MD simulations in combination with the Jarzynski relation. Using these optimized parameters we observed spontaneous folding of a short peptide. The coarse-grained beta-roll, as well as a much larger stack (a fiber) of beta-rolls, were found to be stable. Moreover, the predicted fiber persistence length is in agreement with experiment. The efficacy of the mapping of a coarse-grained system onto an all-atom simulation is discussed. 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.
影响因子：
4.4
作者：
Park, S;Schulten, K
通讯作者：
Schulten, K
蛋白质重折叠与聚集：中等分辨率蛋白质模型的计算机模拟。
DOI：
10.1006/jmbi.2001.4845
发表时间：
2001
期刊：
Journal of molecular biology.
影响因子：
--
作者：
Smith,AV;Hall,CK
通讯作者：
Hall,CK