Qin Sanbo, Zhou Huan-Xiang
Department of Physics and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, USA.
J Phys Chem Lett. 2013 Oct 17;4(20). doi: 10.1021/jz401817x.
Due to their conformational malleability, intrinsically disordered proteins (IDPs) are particularly susceptible to influences of crowded cellular environments. Here we report a computational study of the effects of macromolecular crowding on the conformational ensemble of a coarse-grained IDP model, by using two approaches. In one, the IDP is simulated along with the crowders; in the other, crowder-free simulations are postprocessed to predict the conformational ensembles under crowding. We found significant decreases in the radius of gyration of the IDP under crowding, and suggest repulsive interactions with crowders as a common cause for chain compaction in a number of experimental studies. The postprocessing approach accurately reproduced the conformational ensembles of the IDP in the direct simulations here, and holds enormous potential for realistic modeling of IDPs under crowding, by permitting thorough conformation sampling for the proteins even when they and the crowders are both represented at the all-atom level.
由于其构象可塑性，内在无序蛋白（IDP）特别容易受到拥挤细胞环境的影响。在此，我们通过两种方法报告了一项关于大分子拥挤对粗粒度IDP模型构象集合影响的计算研究。一种方法是将IDP与拥挤剂一起模拟；另一种方法是对无拥挤剂的模拟进行后处理，以预测拥挤条件下的构象集合。我们发现拥挤条件下IDP的回转半径显著减小，并提出与拥挤剂的排斥相互作用是许多实验研究中链压缩的常见原因。后处理方法在此处的直接模拟中准确地再现了IDP的构象集合，并且通过允许对蛋白质进行彻底的构象采样，即使蛋白质和拥挤剂都以全原子水平表示，也为拥挤条件下IDP的实际建模具有巨大潜力。
