FORCE INDUCED UNFOLDING OF TITIN IMMUNOGLOBULIN DOMAINS

力诱导肌联蛋白免疫球蛋白结构域的展开

• 批准号: 6469380
• 负责人: HUI LU
• 金额: $ 6.87万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6469380
• 关键词: biomedical resource; computers; enzymes; model design /development; musculoskeletal system; structural biology; technology /technique

To characterize the dynamic behavior of calmodulin in solution, we have carried out molecular dynamics (MD) simulations of the Ca2+-loaded structure* (see reference [91]). The crystal structure of calmodulin was placed in a solvent sphere of radius 44E, and 6 Cl- and 22 Na+ ions were included to neutralize the system and to model a 150 mM salt concentration. The total number of atoms was 32,867. During the 3 ns simulation the structure exhibits large conformational changes on the nanosecond time scale. The central alpha-helix, which has been shown to unwind locally upon binding of calmodulin to target proteins, bends and unwinds near residue Arg74. We interpret this result as a preparative step in the more extensive structural transition observed in the "flexible linker" region 74-82 of the central helix upon complex formation. The major structural change is a reorientation of the two Ca2+-binding domains with respect to each other and a rearrangement of alpha-helices i n the N-terminus domain which make the hydrophobic target peptide binding site more accessible. This structural rearrangement brings the domains to a more favorable position for target binding, poised to achieve the orientation observed in the complex of calmodulin with myosin-light-chain-kinase. Analysis of solvent structure reveals an inhomogeneity in the mobility of water in the vicinity of the protein which is attributable to the hydrophobic effect exerted by calmodulin's binding sites for target peptides.

为了表征溶液中钙调蛋白的动态行为，我们 已经进行了分子动力学（MD）模拟 CA2+负载结构*（请参阅参考[91]）。 晶体结构 将钙调蛋白放在半径44e的溶剂球中，以及6个Cl-和6 包括22个Na+离子以中和系统并建模150 MM盐浓度。 原子的总数为32,867。 期间 3 NS模拟结构表现出大构象 纳秒时间尺度的变化。 中央α-螺旋，它 在钙调蛋白与靶标结合后，已被证明可以在本地放松 蛋白质，弯曲和放松在残留物arg74附近。 我们解释了这一点 结果是更广泛的结构的准备步骤 在“灵活的接头”区域74-82中观察到的过渡 复合形成时中央螺旋。 主要结构性变化是 相对于每个两个Ca2+结合域的重新定位 N-Terminus域的其他和重新排列的α-螺旋。 这使疏水靶肽结合位点更多 可访问。 这种结构重排将域带到 目标绑定更有利的位置，准备实现 在与 肌球蛋白光链 - 激酶。 溶剂结构的分析揭示了 蛋白质附近水流动性的不均匀性 这归因于由 钙调蛋白的结合位点用于靶肽。