Additional biological protection; blood brain barrier (BBB) to neuronal tissue is essential against invading infections and unwanted chemicals. However, such highly selective transport across the BBB often restricts entry of majority of drug molecules intended for various therapies including thrombotic cerebral ischemia. The inadequate permeation of drugs across BBB and subsequently failure of intended therapies result in finding an effective native transport mechanism. The computational approach in studying protein–protein interactions emerged as one of prospective hope for the identification of proteins (receptors/transporter) towards an effective drug delivery system. Interestingly, low-density lipoprotein receptor proteins-1 (LRP-1) express constitutively in many tissues including BBB plays an important role in the transport of peptides (hormones) believed a candidate transporter for drugs to the neuronal tissue. In this study, earthworm fibrinolytic enzyme (EFE); an effective thrombolyte and its interaction with LRP-1 suggests potential transport mechanism towards entry of drug molecule into neuronal tissue. Fibrinolytic enzyme (PDB Id-1M9U) was docked to LRP1 (PDB Id-1CR8) using Auto Dock tool. Virtual screening following by binding energy calculations suggest a promising interaction of EFE with LRP-1. Further, RMSD and RMSF calculations provide insights and extent of protein-protein interactions (PPIs). Molecular dynamic simulation (MDS) studies were carried out to predict the stability of docked cluster followed by binding mode and surface analysis. Interacting residues in various site/pose were compared with Novel LRP-1 binding peptide 57 and does not show significant similarity. The interacting residues and docking pose in docked cluster suggest LRP-1 a potential transport shuttle for the clot-dissolving drug molecules. We analyzed EFE-LRP-1 interaction and propose LPR-1 mediated endocytosis of EFE across BBB.

额外的生物保护；对神经元组织的血脑屏障（BBB）对于防止感染和有害化学物质至关重要。但是，这种穿过BBB的高度选择性转运通常会限制旨在用于各种治疗方法（包括血栓性脑缺血）的大多数药物分子的进入。药物在血脑屏障中的渗透不足以及随后的预期治疗失败导致寻找有效的天然转运机制。研究蛋白质与蛋白质相互作用的计算方法已成为鉴定蛋白质（受体/转运蛋白）朝向有效药物输送系统的前途希望之一。有趣的是 低密度脂蛋白受体蛋白1（LRP-1）在包括BBB在内的许多组织中组成性表达，在肽（激素）的运输中起着重要作用，据信这种药物是药物向神经元组织的候选转运蛋白。在这项研究中，worm纤溶酶（EFE）；有效的血栓溶解液及其与LRP-1的相互作用提示了药物分子进入神经元组织的潜在转运机制。使用Auto Dock工具将纤溶酶（PDB Id-1M9U）对接至LRP1（PDB Id-1CR8）。结合能量计算进行的虚拟筛选表明，EFE与LRP-1有良好的相互作用。此外，RMSD和RMSF计算提供了洞察力和蛋白质-蛋白质相互作用（PPI）的程度。进行了分子动力学模拟（MDS）研究，以预测对接簇的稳定性，然后进行结合模式和表面分析。将各种位点/姿势中的相互作用残基与新型LRP-1结合肽57进行比较，但未显示出明显的相似性。相互作用的残基和对接簇中的对接姿势表明LRP-1是溶解血块的药物分子的潜在转运穿梭体。我们分析了EFE-LRP-1的相互作用，并提出了LPR-1介导的EFE跨BBB的内吞作用。