Unfolding of titin domains studied by molecular dynamics simulations
Unfolding of titin domains studied by molecular dynamics simulations
复制标题
DOI：
10.1023/a:1023466608163
复制
发表时间：
2002-01-01
影响因子：
2.7
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Gao, M;Lu, H;Schulten, K
肌联蛋白，一种在横纹肌肌原纤维中发现的类似于1 μ m长的蛋白质，具有独特的弹性。在原子力显微镜和光镊实验中已经证明了肌联蛋白的可延伸行为涉及单个免疫球蛋白样（IG）结构域的可逆解折叠。我们使用一种新的计算机模拟方法--转向分子动力学（SMD）来研究单肌联蛋白IG结构域在应力作用下的力学响应。拉伸IG域I1和I27的模拟已经在明确的水分子的溶剂中进行。SMD方法提供了IG域如何对外力作出反应的详细结构和动态描述。SMD结果的验证包括与AFM记录的定性和定量一致性。此外，SMD与单分子实验数据相结合，导致全面了解IG域的机械性能。连接结构域末端β链的一组骨架氢键在对外力的机械抵抗中起着关键作用。结构上的微小差异允许I27的机械展开中间体，但不允许II。I27的重折叠模拟展示了锁定机制。
Titin, a similar to1 mum long protein found in striated muscle myofibrils, possesses unique elastic properties. The extensible behavior of titin has been demonstrated in atomic force microscopy and optical tweezer experiments to involve the reversible unfolding of individual immunoglobulin-like (Ig) domains. We have used steered molecular dynamics (SMD), a novel computer simulation method, to investigate the mechanical response of single titin Ig domains upon stress. Simulations of stretching Ig domains I1 and I27 have been performed in a solvent of explicit water molecules. The SMD approach provides a detailed structural and dynamic description of how Ig domains react to external forces. Validation of SMD results includes both qualitative and quantitative agreement with AFM recordings. Furthermore, combining SMD with single molecule experimental data leads to a comprehensive understanding of Ig domains' mechanical properties. A set of backbone hydrogen bonds that link the domains' terminal beta-strands play a key role in the mechanical resistance to external forces. Slight differences in architecture permit a mechanical unfolding intermediate for I27, but not for II. Refolding simulations of I27 demonstrate a locking mechanism.