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首页> 外文会议>Symposium QQ on Biological Materials and Structures in Physiologically Extreme Conditions and Disease >Computational multiscale studies of collagen tissues in the context of brittle bone disease osteogenesis imperfecta
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Computational multiscale studies of collagen tissues in the context of brittle bone disease osteogenesis imperfecta

机译：脆性骨病骨质型骨质骨质骨质骨质骨质型胶原蛋白组织的计算多尺度研究

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Osteogenesis imperfecta (abbreviated as OI) is a genetic disorder in collagen characterized by mechanically weakened tendon, fragile bones, skeletal deformities and in severe cases prenatal death. Even though many studies have attempted to associate specific mutation types with phenotypic severity, the molecular and mesoscale mechanisms by which a single point mutation influences the mechanical behavior of tissues at multiple length-scales remain unknown. Here we review results of a hierarchy of full atomistic and mesoscale simulations that demonstrated that OI mutations severely compromise the mechanical properties of collagenous tissues at multiple scales, from single molecules to collagen fibrils. Notably, mutations that lead to the most severe OI phenotype correlate with the strongest effects, leading to weakened intermolecular adhesion, increased intermolecular spacing, reduced stiffness, as well as a reduced failure strength of collagen fibrils (Gautieri et al., Biophys. J., 2009). Our study explains how single point mutations can control the breakdown of tissue at much larger length-scales, a question of great relevance for a broad class of genetic diseases. Furthermore, by extending the MARTINI coarse-grained force field, we provide a new modeling tool to study collagen molecules and fibrils at much larger scales than accessible to existing full atomistic models, while incorporating key chemical and mechanical features and thereby presents a powerful approach to computational materiomics (Gautieri et al., Journal of Chemical Theory and Computation, 2010). We describe the coarse-graining approach and present preliminary findings based on this model in applying it to large-scale models of molecular assemblies into fibrils.
机译：骨质发生不完全（缩写为OI）是胶原蛋白的遗传疾病，其特征在于机械弱化肌腱，脆弱的骨骼，骨骼畸形以及严重案例前死亡。尽管许多研究已经尝试将特定突变类型与表型严重程度相关联，但是单点突变在多个长度尺度下影响组织的机械行为的分子和介质机制仍然未知。在这里，我们审查了完全原子和Messcale模拟的等级的结果，证明了OI突变严重损害了多个尺度的胶原组织的机械性能，从单个分子到胶原型原纤维。值得注意的是，导致最严重的OI表型的突变与最强的效果相关，导致分子间粘附弱，分子间间距增加，降低刚度以及胶原型原纤维的降低的失效强度（Gautieri等，Biophys。J. ，2009）。我们的研究解释了单点突变如何控制组织的细分，更大的长度，对广泛类别的遗传疾病具有重要相关性的问题。此外，通过延长Martini粗粒强制领域，我们提供了一种新的建模工具，用于研究胶原蛋白分子和原纤维，比现有的完整原子模型可通过可访问，同时包含关键的化学和机械特征，从而提出了一种强大的方法计算产物（Gautieri等，中国化学理论和计算杂志，2010）。我们描述了基于该模型的粗谷物方法和初步发现，在将其施加到原纤维中的大规模模型。

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