MD trajectories demonstrating the role of stochastic resonance in triggering the EPCR-Vorapaxar unbinding.

MD trajectory of simulation of the extracellular domain of EPCR with bound PCGla domain and two Vorapaxar (VPX) ligands.The EPCR-ligands system simulated at 10 degrees for 10 ns at 1 THz sampling rate allowed to observe partial unbinding of VPX. Two regions of VPX (carbamic acid tail and central naphtho-furan containing regions) were detached from EPCR b-sheet, while fluorophenyl-pyridin region of VPX bound to b-sheet remained in contact with EPCR. The trajectory of the same system simulated at 37 degrees demonstrated that all three fragments of VPX remained in contact with EPCR, although local reorientation of VPX was observed. VPX bound in the hydrophobic cleft of EPCR formed by two a-helices remained in contact with EPCR at both temperatures at all times with occasional reorientation of bound molecule. The system contained 53650 atoms including EPCR, PCGla domain, two VPX molecules, and water molecules.NAMD software and CHARMM36m improved force field with TIP3 water model were used for simulations. The original trajectories were saved with stride 4, to generate the uploaded 1.6 GB trajectory files (epcr_gla_2vpx2500ts_10degr.dcd and epcr_gla_2vpx2500ts_37degr.dcd) each containing 2500 time steps. Protein structure files corresponding to the trajectory files are epcr_gla_2vpx2500ts_10degr.psf and epcr_gla_2vpx2500ts_37degr.psf, respectively.本数据集为结合了PCGla结构域与两个沃拉帕沙（Vorapaxar, VPX）配体的内皮细胞蛋白C受体（Endothelial Protein C Receptor, EPCR）胞外域的分子动力学（Molecular Dynamics, MD）模拟轨迹。该EPCR-配体体系在10摄氏度下进行了10纳秒的模拟，采样速率为1太赫兹（THz），观测到VPX发生了部分解离。VPX的两个区域（氨基甲酸尾部与含中心萘呋喃的区域）从EPCR的β折叠片层上脱离，而结合在β折叠片层上的VPX氟苯基吡啶区域仍与EPCR保持接触。在37摄氏度下模拟的同一体系的轨迹则显示，尽管VPX发生了局部重取向，但其全部三个片段仍与EPCR保持接触。结合在由两个α螺旋构成的EPCR疏水裂隙中的VPX，在两种温度下始终与EPCR保持接触，仅偶尔发生结合分子的重取向。 该体系共包含53650个原子，涵盖EPCR、PCGla结构域、两个VPX分子与水分子。模拟采用NAMD软件，以及搭载TIP3水模型的改进型CHARMM36m力场。原始轨迹以步幅4进行保存，由此生成了本次上传的两个1.6GB轨迹文件：epcr_gla_2vpx2500ts_10degr.dcd与epcr_gla_2vpx2500ts_37degr.dcd，每个文件均包含2500个时间步。与上述轨迹文件对应的蛋白质结构文件分别为epcr_gla_2vpx2500ts_10degr.psf与epcr_gla_2vpx2500ts_37degr.psf。