Molecular Simulation Of Several Important Protein-protein Interactions

TLR5is a pattern-recognition receptor of the immune system and recognizes bacterial flagellin. In the further research TLR5agonist flagellin showed radioprotective activity by activating NF-κB signaling, which could be used in improving the therapeutic index of cancer radiotherapy and served as biological protectants in radiation emergencies. In this study, homology modeling was applied to predict the three-dimensional structure of TLR5, then the optimized model was evaluated. The results showed that the model was reliable. At last docking studies were performed and the most promising complex was picked. The free energy calculation showed that VDW and electrostatic energies were major favorable contributions to the binding, and R392/D393of TLR5were the most essential in the binding.Tumstatin T7peptide, which has obviously anti-angiogenic and induced endothelial cell apoptosis activity, is an endogenous angiogenesis inhibitor from the Col IV. T7peptide inhibits the angiogenesis by combining with the αvβ3integrin. Double effects of anti-angiogenic and inhibiting tumor cell proliferation make T7peptide as potential antitumor activity. In this work, folding simulation of T7peptide was completed firstly, then docking in conjunction with molecular dynamics simulation was used to explore the binding mode of T7peptide and αvβ3integrin. The binding mode analysis revealed that the residues Ser90, Arg91, Asp93and Tyr94in T7peptide were most likely the key interaction sites. The hydroxyl of Tyr94coordinates αvβ3via a Mn2+ion, revealing that Mn2+is also an important factor for the interaction.