The accumulation of advanced glycation end‐products is a fundamental process that is central to age‐related decline in musculoskeletal tissues and locomotor system function and other collagen‐rich tissues. However, although computational studies of advanced glycation end‐product cross‐links could be immensely valuable, this area remains largely unexplored given the limited availability of structural parameters for the derivation of force fields for Molecular Dynamics simulations. In this article, we present the bonded force constants, atomic partial charges and geometry of the arginine‐lysine cross‐links DOGDIC, GODIC, and MODIC. We have performed in vacuo Molecular Dynamics simulations to validate their implementation against quantum mechanical frequency calculations. A DOGDIC advanced glycation end‐product cross‐link was then inserted into a model collagen fibril to explore structural changes of collagen and dynamics in interstitial water. Unlike our previous studies of glucosepane, our findings suggest that intra‐collagen DOGDIC cross‐links furthers intra‐collagen peptide hydrogen‐bonding and does not promote the diffusion of water through the collagen triple helices.

中文翻译：

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赖氨酸-精氨酸晚期糖基化终产物交联和对胶原结构的影响：分子动力学研究

晚期糖基化终产物的积累是一个基本过程，它是肌肉骨骼组织和运动系统功能以及其他富含胶原蛋白的组织与年龄相关的衰退的核心。然而，尽管高级糖基化终产物交联的计算研究可能非常有价值，但鉴于用于推导分子动力学模拟的力场的结构参数的可用性有限，该领域在很大程度上仍未被探索。在本文中，我们介绍了精氨酸-赖氨酸交联 DOGDIC、GODIC 和 MODIC 的键合力常数、原子部分电荷和几何形状。我们已经在真空分子动力学模拟中进行了验证，以根据量子力学频率计算来验证它们的实现。然后将 DOGDIC 晚期糖基化终产物交联插入模型胶原纤维中，以探索胶原蛋白的结构变化和间质水中的动力学。与我们之前对葡萄糖的研究不同，我们的研究结果表明，胶原内 DOGDIC 交联进一步促进了胶原内肽的氢键结合，并且不会促进水通过胶原三螺旋的扩散。