title: [alphaIIbbeta3 modeling simulation and design of the cyclic RGD].
abstract: Integrin alphaIIbbeta3 of the platelet surfaces regulates the thrombosis formation. alphaIIbbeta3 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 alphaIIbbeta3 using homology-modeling (modeller8v2 software), with integrin alphavbeta3 (pdb code 1JV2) as the template. Accordingly, a cyclic RGD(RGD-c) peptide was designed to bind alphaIIbbeta3 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 alphaIIbbeta3 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 alphaIIbbeta3 antagonists.
authors.affiliation: College of Physics, Nankai University, Tianjin 300071, China.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Luo
authors.forename: Meizong
authors.initials: M
authors.lastname: Chen
authors.forename: Imshik
authors.initials: I
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C047981:arginyl-glycyl-aspartic acid