αIIbβ3 Modeling Simulation and Design of Cyclic RGD Peptide

Integrin αIIbβ3 of the platelet surfaces regulates the thrombosis formation. αIIbβ3 binds to the RGD sequence (Arg-Gly-Asp) of fibrinogen, promotes the platelet aggregation and finally leads to the thrombus. We obtained the three-dimensional molecular structure of αIIbβ3 using homology-modeling (modeller8v2 software), with integrin αvβ3 (pdb code 1JV2) as the template. Accordingly, a cyclic RGD(RGD-c) peptide was designed to bind αIIbβ3 as an antagonist and to block the formation of thrombus. We added two amino acids X, Y to both sides of RGD-c. X and Y could bind to each other by disulfide bond that finally made RGD-c a cyclic peptide. The optimum structure of RGD-c was obtained from the energetic optimization processes. All amino acids were placed at the X and Y to conduct molecular docking to the integrin αIIbβ3. We got the optimum structure of RGD-c by energetic optimization and the antagonistic combination analysis. The results might provide an insight into designing and screening integrin αIIbβ3 antagonists.