NASA Ames Research Center, Moffett Field, CA, 94043, USA.
Molecular Therapeutics and Formulation, School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
Sci Rep. 2019 Aug 15;9(1):11873. doi: 10.1038/s41598-019-47337-8.
Diffusional motion within the crowded environment of the cell is known to be crucial to cellular function as it drives the interactions of proteins. However, the relationships between protein diffusion, shape and interaction, and the evolutionary selection mechanisms that arise as a consequence, have not been investigated. Here, we study the dynamics of triaxial ellipsoids of equivalent steric volume to proteins at different aspect ratios and volume fractions using a combination of Brownian molecular dynamics and geometric packing. In general, proteins are found to have a shape, approximately Golden in aspect ratio, that give rise to the highest critical volume fraction resisting gelation, corresponding to the fastest long-time self-diffusion in the cell. The ellipsoidal shape also directs random collisions between proteins away from sites that would promote aggregation and loss of function to more rapidly evolving nonsticky regions on the surface, and further provides a greater tolerance to mutation.
细胞中拥挤环境下的扩散运动对细胞功能至关重要，因为它驱动了蛋白质的相互作用。然而，蛋白质扩散、形状和相互作用之间的关系，以及由此产生的进化选择机制，尚未得到研究。在这里，我们使用布朗分子动力学和几何包装的组合，研究了不同纵横比和体积分数的三轴椭球体的动力学。一般来说，蛋白质的形状接近黄金纵横比，这导致了最高的临界体积分数，抵抗凝胶化，对应于细胞中最快的长时间自扩散。椭球形状还将蛋白质之间的随机碰撞引导到远离促进聚集和功能丧失的部位，而更快速进化的非粘性表面区域，并且进一步提供了对突变的更大容忍度。
