Energy minimized crystal structures of P-selectins based on molecular dynamics simulation: leading to two average structures capable of designing anti-thrombotic agents
Energy minimized crystal structures of P-selectins based on molecular dynamics simulation: leading to two average structures capable of designing anti-thrombotic agents
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DOI：
10.1039/c3md00004d
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发表时间：
2013-06
期刊：
影响因子：
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通讯作者：
Haimei Zhu;Wang Yuji;Ming Zhao;Jianhui Wu;Xiaoyi Zhang;Guodong Yang;Shiqi Peng
中科院分区：
文献类型：
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作者：
Haimei Zhu;Wang Yuji;Ming Zhao;Jianhui Wu;Xiaoyi Zhang;Guodong Yang;Shiqi Peng
在最常见的心血管事件中，深静脉血栓形成一直是发病率和死亡率最突出的原因之一。可溶性P-选择素在血栓形成中起重要作用，一直被认为是抗血栓药物的靶点。在分子模拟方面，本文对不同的P-选择素结构进行了理论研究。通过从PDB 1G1R中去除SLeX或从PDB 1G1S中去除SLeX和PSGL-1，最小化形成的结构的能量，并进行分子动力学模拟，得到了P-选择素的两种平均结构。通过主链RMSD值、RMSF值、二级结构的变化、构象柔性区和相关运动等一系列反映两种平均结构质量的性质的比较，表明两种平均结构都适用于抗血栓药物的设计，而且同等重要。
In the most frequent cardiovascular events, deep vein thrombosis has been one of the most prominent causes of morbidity and mortality. Soluble P-selectin plays an essential role in the formation of thrombosis and has been considered a target of anti-thrombotic agents. With regard to molecular modeling, here the theoretical studies were performed on variant P-selectin structures. By removing SLex from PDB 1G1R or removing both SLex and PSGL-1 from PDB 1G1S, minimizing the energy of the formed structures, and performing molecular dynamics simulations, two average structures of P-selectins were obtained. A series of comparisons of the properties reflecting the quality of the two average structures, such as the backbone RMSD values, RMSF values, the change of the secondary structures, the conformation flexible regions and the correlated motions demonstrated that both of the two average structures are suitable and equally important for anti-thrombotic agent design.