Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055, China.
Department of Chemistry & Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
J Chem Theory Comput. 2017 Aug 8;13(8):3936-3944. doi: 10.1021/acs.jctc.7b00383. Epub 2017 Jul 17.
We introduce Replica-Exchange-with-Tunneling (RET) simulations as a tool for studies of the conversion between polymorphic amyloids. For the 11-residue amyloid-forming cylindrin peptide we show that this technique allows for a more efficient sampling of the formation and interconversion between fibril-like and barrel-like assemblies. We describe a protocol for optimized analysis of RET simulations that allows us to propose a mechanism for formation and interconversion between various cylindrin assemblies. Especially, we show that an interchain salt bridge between residues K3 and D7 is crucial for formation of the barrel structure.
我们介绍 Replica-Exchange-with-Tunneling (RET) 模拟作为研究多态淀粉样转化的工具。对于 11 残基的淀粉样形成的圆柱蛋白肽，我们表明该技术允许更有效地采样原纤维样和桶状组装之间的形成和相互转化。我们描述了一种优化 RET 模拟分析的协议，该协议使我们能够提出圆柱蛋白组装体之间形成和相互转化的机制。特别是，我们表明残基 K3 和 D7 之间的链间盐桥对于桶状结构的形成至关重要。
