Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation
Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation
复制标题
DOI：
10.1016/s0006-3495(98)77556-3
复制
发表时间：
1998-08-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Lu, H;Isralewitz, B;Schulten, K
肌联蛋白是横纹肌肌原纤维中发现的一种 1 μm 长的蛋白质，其 I 带区域具有独特的弹性和可伸展性，该区域主要由 PEVK 区域（70% 脯氨酸、谷氨酸、缬氨酸和赖氨酸残基）和七链 β 夹心免疫球蛋白 (Ig) 结构域组成。原子力显微镜和光镊实验表明，肌动蛋白作为多级熵弹簧的行为部分取决于单个 Ig 结构域的可逆展开。我们进行了引导分子动力学模拟，以 0.5 和 1.0 埃/ps 的拉伸速度在溶液中拉伸单肌联 Ig 结构域。由此产生的力延伸曲线显示每个 Ig 结构域展开的单个主峰，与实验观察到的 Ig 结构域在外部拉伸力下的顺序展开一致，而不是一致展开。该力峰值可归因于主链氢键的初始爆发，该氢键发生在反平行 β 链 A 和 B 之间以及平行 p 链 A' 和 G 之间。模拟的其他特征，包括力峰值的位置和不同 Ig 结构域的相对展开阻力，可以与实验观察结果相关。
Titin, a 1-mu m-long protein found in striated muscle myofibrils, possesses unique elastic and extensibility properties in its I-band region, which is largely composed of a PEVK region (70% proline, glutamic acid, valine, and lysine residue) and seven-strand beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin as a multistage entropic spring has been shown in atomic force microscope and optical tweezer experiments to partially depend on the reversible unfolding of individual Ig domains. We performed steered molecular dynamics simulations to stretch single titin Ig domains in solution with pulling speeds of 0.5 and 1.0 Angstrom/ps. Resulting force-extension profiles exhibit a single dominant peak for each Ig domain unfolding, consistent with the experimentally observed sequential, as opposed to concerted, unfolding of Ig domains under external stretching forces. This force peak can be attributed to an initial burst of backbone hydrogen bonds, which takes place between antiparallel beta-strands A and B and between parallel p-strands A' and G. Additional features of the simulations, including the position of the force peak and relative unfolding resistance of different Ig domains, can be related to experimental observations.