Laboratoire de Biochimie Théorique (UPR 9080), CNRS, Université de Paris, 13 rue Pierre et Marie Curie, Paris, 75005, France.
Institut de Biologie Physico-Chimique, Fondation Edmond de Rothschild, PSL Research University, 13 rue Pierre et Marie Curie, Paris, 75005, France.
J Phys Chem B. 2023 Apr 27;127(16):3616-3623. doi: 10.1021/acs.jpcb.3c00253. Epub 2023 Apr 18.
Macromolecular crowding has profound effects on the mobility of proteins, with strong implications on the rates of intracellular processes. To describe the dynamics of crowded environments, detailed molecular models are needed, capturing the structures and interactions arising in the crowded system. In this work, we present OPEPv7, which is a coarse-grained force field at amino-acid resolution, suited for rigid-body simulations of the structure and dynamics of crowded solutions formed by globular proteins. Using the OPEP protein model as a starting point, we have refined the intermolecular interactions to match the experimentally observed dynamical slowdown caused by crowding. The resulting force field successfully reproduces the diffusion slowdown in homogeneous and heterogeneous protein solutions at different crowding conditions. Coupled with the lattice Boltzmann technique, it allows the study of dynamical phenomena in protein assemblies and opens the way for the in silico rheology of protein solutions.
大分子拥挤对蛋白质的流动性有深远的影响，对细胞内过程的速率有强烈的影响。为了描述拥挤环境的动力学，需要详细的分子模型，捕捉在拥挤系统中出现的结构和相互作用。在这项工作中，我们提出了 OPEPv7，这是一个氨基酸分辨率的粗粒化力场，适合于球形蛋白质形成的拥挤溶液的结构和动力学的刚体模拟。我们使用 OPEP 蛋白质模型作为起点，对分子间相互作用进行了细化，以匹配拥挤引起的实验观察到的动力学减速。所得力场成功地再现了不同拥挤条件下均匀和非均匀蛋白质溶液中的扩散减速。与格子玻尔兹曼技术相结合，它允许研究蛋白质组装中的动力学现象，并为蛋白质溶液的计算机流变学开辟了道路。
