Sotomayor Marcos, Schulten Klaus
Department of Physics, University of Illinois at Urbana-Champaign, and Beckman Institute for Advanced Science and Technology, 405 North Mathews Avenue, Urbana, IL 61801, USA.
Science. 2007 May 25;316(5828):1144-8. doi: 10.1126/science.1137591.
Single-molecule force experiments in vitro enable the characterization of the mechanical response of biological matter at the nanometer scale. However, they do not reveal the molecular mechanisms underlying mechanical function. These can only be readily studied through molecular dynamics simulations of atomic structural models: "in silico" (by computer analysis) single-molecule experiments. Steered molecular dynamics simulations, in which external forces are used to explore the response and function of macromolecules, have become a powerful tool complementing and guiding in vitro single-molecule experiments. The insights provided by in silico experiments are illustrated here through a review of recent research in three areas of protein mechanics: elasticity of the muscle protein titin and the extracellular matrix protein fibronectin; linker-mediated elasticity of the cytoskeleton protein spectrin; and elasticity of ankyrin repeats, a protein module found ubiquitously in cells but with an as-yet unclear function.
体外单分子力实验能够在纳米尺度上表征生物物质的力学响应。然而，它们并未揭示机械功能背后的分子机制。这些机制只能通过原子结构模型的分子动力学模拟来轻松研究：即“计算机模拟”（通过计算机分析）单分子实验。在分子动力学模拟中，外力被用于探索大分子的响应和功能，它已成为一种强大的工具，可补充和指导体外单分子实验。本文通过回顾蛋白质力学三个领域的近期研究，阐述了计算机模拟实验所提供的见解：肌肉蛋白肌联蛋白和细胞外基质蛋白纤连蛋白的弹性；细胞骨架蛋白血影蛋白的接头介导弹性；以及锚蛋白重复序列的弹性，锚蛋白重复序列是一种在细胞中普遍存在但功能尚不清楚的蛋白质模块。
