Coarse-Grained Model of Collagen Molecules Using an Extended MARTINI Force Field
Coarse-Grained Model of Collagen Molecules Using an Extended MARTINI Force Field
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DOI：
10.1021/ct100015v
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发表时间：
2010-04-01
影响因子：
5.5
通讯作者：
Buehler, Markus J.
中科院分区：
文献类型：
--
作者：
Gautieri, Alfonso;Russo, Antonio;Buehler, Markus J.
胶原蛋白是人体中最丰富的蛋白质，为肌腱、韧带和骨骼等结缔组织提供机械稳定性、弹性和强度。在这里，我们报告了一个扩展的MARTINI粗粒力场，最初开发的脂质，蛋白质和碳水化合物，用于描述胶原蛋白分子的结构和机械性能。我们确定MARTINI力场参数来描述羟脯氨酸氨基酸残基和胶原蛋白中发现的三螺旋构象结构。我们验证了扩展的MARTINI模型，通过直接分子动力学模拟的杨氏模量的短8 nm长的胶原蛋白样分子，导致约4 GPa的值，与早期的全原子模拟明确的溶剂以及实验结果的良好一致性。我们还应用扩展的MARTINI模型来模拟一个300 nm长的人I型胶原蛋白分子的实际氨基酸序列，并计算其持久性长度从分子动力学轨迹。我们得到的值为51.5 +/- 6.7 nm的持久性长度，这是早期的实验结果的范围内。我们的工作扩展了胶原组织的分子模型的适用性，通过提供一个建模工具来研究胶原分子和原纤维在比现有的全原子模型更大的尺度上，同时结合关键的化学和机械特征，从而提出了一个强大的方法来计算材料组学。
Collagen is the most abundant protein in the human body, providing mechanical stability, elasticity, and strength to connective tissues such as tendons, ligaments, and bone. Here, we report an extension of the MARTINI coarse-grained force field, originally developed for lipids, proteins, and carbohydrates, used to describe the structural and mechanical properties of collagen molecules. We identify MARTINI force field parameters to describe hydroxyproline amino acid residues and for the triple helical conformational structure found in collagen. We validate the extended MARTINI model through direct molecular dynamics simulations of Young's modulus of a short 8-nm-long collagen-like molecule, resulting in a value of approximately 4 GPa, in good agreement with earlier full atomistic simulations in explicit solvent as well as experimental results. We also apply the extended MARTINI model to simulate a 300-nm-long human type I collagen molecule with the actual amino acid sequence and calculate its persistence length from molecular dynamics trajectories. We obtain a value of 51.5 +/- 6.7 nm for the persistence length, which is within the range of earlier experimental results. Our work extends the applicability of molecular models of collagenous tissues by providing a 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 presenting a powerful approach to computational materiomics.