Steered molecular dynamics studies of titin I1 domain unfolding
Steered molecular dynamics studies of titin I1 domain unfolding
复制标题
DOI：
10.1016/s0006-3495(02)75343-5
复制
发表时间：
2002-12-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Gao, M;Wilmanns, M;Schulten, K
心肌蛋白质Titin负责肌肉的被动弹性和伸展性，在其I带区域具有约40个免疫球蛋白样域。原子力显微镜(AFM)和导向分子动力学(SMD)被成功地结合起来研究单个Ig结构域的可逆展开。然而，以前对Titin I带模块的SMD研究仅限于I27，这是唯一结构上已知的来自Titin I带远端区域的Ig结构域。在本文中，我们报告了SMID模拟展开I1，第一个结构上可用的Ig结构域，从Titin I-带的近端区域。这些模拟是为了即将到来的原子力显微镜实验而进行的。用恒速和恒力拉伸来模拟氧化的I1和还原的I1的机械去折叠，氧化的I1具有连接β链C和E的二硫键，而还原的I1中没有二硫键。模拟表明，I1主要通过其A和Bβ链之间的6个链间氢键来保护其免受外部应力的影响。二硫键通过限制A‘-链和G-链之间主干氢键的断裂来提高氧化I1结构域的机械稳定性。二硫键还将I1的最大扩展限制在与220埃相似的范围。比较了I1和I27的展开途径，并讨论了对AFM实验的意义。
The cardiac muscle protein titin, responsible for developing passive elasticity and extensibility of muscle, possesses about 40 immunoglobulin-like (Ig) domains in its I-band region. Atomic force microscopy (AFM) and steered molecular dynamics (SMD) have been successfully combined to investigate the reversible unfolding of individual Ig domains. However, previous SMD studies of titin I-band modules have been restricted to I27, the only structurally known Ig domain from the distal region of the titin I-band. In this paper we report SMID simulations unfolding I1, the first structurally available Ig domain from the proximal region of the titin I-band. The simulations are carried out with a view toward upcoming atomic force microscopy experiments. Both constant velocity and constant force stretching have been employed to model mechanical unfolding of oxidized I1, which has a disulfide bond bridging beta-strands C and E, as well as reduced I1, in which the disulfide bridge is absent. The simulations reveal that I1 is protected against external stress mainly through six interstrand hydrogen bonds between its A and B beta-strands. The disulfide bond enhances the mechanical stability of oxidized I1 domains by restricting the rupture of backbone hydrogen bonds between the A'- and G-strands. The disulfide bond also limits the maximum extension of I1 to similar to220 Angstrom. Comparison of the unfolding pathways of I1 and I27 are provided and implications to AFM experiments are discussed.