1.alphaIIbbeta3 modeling simulation and design of the cyclic RGD.
Mingyan LUO ; Meizong CHEN ; Imshik LEE
Chinese Journal of Biotechnology 2008;24(2):297-301
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.
Amino Acid Sequence
;
Drug Design
;
Humans
;
Models, Molecular
;
Oligopeptides
;
chemistry
;
Platelet Aggregation Inhibitors
;
chemical synthesis
;
chemistry
;
Platelet Glycoprotein GPIIb-IIIa Complex
;
antagonists & inhibitors
;
chemistry