Molecular dynamics simulations of the full triple helical region of collagen type I provide an atomic scale view of the protein's regional heterogeneity.
Molecular dynamics simulations of the full triple helical region of collagen type I provide an atomic scale view of the protein's regional heterogeneity.
复制标题
I 型胶原蛋白完整三螺旋区域的分子动力学模拟提供了蛋白质区域异质性的原子尺度视图。
DOI：
10.1142/9789814335058_0021
复制
发表时间：
2011
影响因子：
--
通讯作者：
Klein,TeriE
中科院分区：
文献类型：
--
作者：
Bodian,DaleL;Radmer,RandallJ;Holbert,Sean;Klein,TeriE
胶原蛋白是一种普遍存在的细胞外基质蛋白。它的生物学功能，包括维持组织的结构完整性，取决于它的多尺度，层次结构。三个>1000个氨基酸的伸长的、扭曲的肽链各自组装成三聚体蛋白质，其特征在于限定的三螺旋结构域。三聚体结合成原纤维，然后聚集成纤维。我们进行了10纳秒的全长三螺旋结构域，这是计算上可行的分割成重叠片段的蛋白质的分子动力学模拟。该计算包括约180万个原子，包括溶剂，使用超过25万台计算机的CPU花费了大约11个月。开发了专门的分析协议和关系数据库，以处理公开提供的大量数据。模拟的结构表现出异质性的三重螺旋结构域与实验结果一致，但在更高的分辨率。这些结构是研究蛋白质高阶形式和模拟疾病相关突变影响的基础。
Collagen is a ubiquitous extracellular matrix protein. Its biological functions, including maintenance of the structural integrity of tissues, depend on its multiscale, hierarchical structure. Three elongated, twisted peptide chains of >1000 amino acids each assemble into trimeric proteins characterized by the defining triple helical domain. The trimers associate into fibrils, which pack into fibers. We conducted a 10 ns molecular dynamics simulation of the full-length triple helical domain, which was made computationally feasible by segmenting the protein into overlapping fragments. The calculation included ~1.8 million atoms, including solvent, and took approximately 11 months using the CPUs of over a quarter of a million computers. Specialized analysis protocols and a relational database were developed to process the large amounts of data, which are publicly available. The simulated structures exhibit heterogeneity in the triple helical domain consistent with experimental results but at higher resolution. The structures serve as the foundation for studies of higher order forms of the protein and for modeling the effects of disease-associated mutations.