Yesudasan Sumith, Wang Xianqiao, Averett Rodney D
School of Chemical, Materials and Biomedical Engineering, University of Georgia, 597 D.W. Brooks Drive, Athens, GA, 30602, USA.
School of Environmental, Civil, Agricultural and Mechanical Engineering, University of Georgia, 597 D.W. Brooks Drive, Athens, GA, 30602, USA.
J Mol Model. 2018 Apr 5;24(5):109. doi: 10.1007/s00894-018-3642-7.
Studies suggest that patients with deep vein thrombosis and diabetes often have hypercoagulable blood plasma, leading to a higher risk of thromboembolism formation through the rupture of blood clots, which may lead to stroke and death. Despite many advances in the field of blood clot formation and thrombosis, the influence of mechanical properties of fibrin in the formation of thromboembolisms in platelet-poor plasma is poorly understood. In this paper, we combine the concepts of reactive molecular dynamics and coarse-grained molecular modeling to predict the complex network formation of fibrin clots and the branching of fibrin monomers. The 340-kDa fibrinogen molecule was converted into a coarse-grained molecule with nine beads, and using our customized reactive potentials, we simulated the formation and polymerization process of a fibrin clot. The results show that higher concentrations of thrombin result in higher branch-point formation in the fibrin clot structure. Our results also highlight many interesting properties, such as the formation of thicker or thinner fibers depending on the thrombin concentration. To the best of our knowledge, this is the first successful molecular polymerization study of fibrin clots to focus on thrombin concentration.
研究表明，深静脉血栓形成和糖尿病患者的血浆通常具有高凝性，这会通过血栓破裂导致血栓栓塞形成的风险增加，进而可能导致中风和死亡。尽管在血栓形成和血栓栓塞领域取得了许多进展，但纤维蛋白的机械性能对血小板贫乏血浆中血栓栓塞形成的影响仍知之甚少。在本文中，我们结合反应分子动力学和粗粒度分子建模的概念，来预测纤维蛋白凝块的复杂网络形成以及纤维蛋白单体的分支。将340 kDa的纤维蛋白原分子转化为具有九个珠子的粗粒度分子，并使用我们定制的反应势，模拟了纤维蛋白凝块的形成和聚合过程。结果表明，较高浓度的凝血酶会导致纤维蛋白凝块结构中形成更多的分支点。我们的结果还突出了许多有趣的特性，例如根据凝血酶浓度形成更粗或更细的纤维。据我们所知，这是首次成功聚焦于凝血酶浓度的纤维蛋白凝块分子聚合研究。
