研究人员探索了从设计的具有内部循环或二面体对称性的轴和转子组件中，重新构建蛋白质机械的问题。研究人员发现，轴-转子系统在体外和体内都能按照设计进行组装。利用冷冻电镜，研究人员发现这些系统填充了构象可变的相对方向，反映了耦合组件的对称性和计算设计的界面能量景观。这些具有内部自由度的机械系统，是朝着设计可遗传编码的纳米机械迈出的一步。
据介绍，自然界的分子机器含有蛋白质成分，它们彼此之间进行相对运动。设计这种具有内部自由度的机械约束的纳米级蛋白质结构，是计算蛋白质设计的一个突出挑战。
附：英文原文
Title: Computational design of mechanically coupled axle-rotor protein assemblies
Author: A. Courbet, J. Hansen, Y. Hsia, N. Bethel, Y.-J. Park, C. Xu, A. Moyer, S. E. Boyken, G. Ueda, U. Nattermann, D. Nagarajan, D. Silva, W. Sheffler, J. Quispe, A. Nord, N. King, P. Bradley, D. Veesler, J. Kollman, D. Baker
Issue&Volume: 2022-04-22
Abstract: Natural molecular machines contain protein components that undergo motion relative to each other. Designing such mechanically constrained nanoscale protein architectures with internal degrees of freedom is an outstanding challenge for computational protein design. Here we explore the de novo construction of protein machinery from designed axle and rotor components with internal cyclic or dihedral symmetry. We find that the axle-rotor systems assemble in vitro and in vivo as designed. Using cryo–electron microscopy, we find that these systems populate conformationally variable relative orientations reflecting the symmetry of the coupled components and the computationally designed interface energy landscape. These mechanical systems with internal degrees of freedom are a step toward the design of genetically encodable nanomachines.
DOI: abm1183
Source: https://www.science.org/doi/10.1126/science.abm1183