alphaIIbbeta3 modeling simulation and design of the cyclic RGD.
- Author:
Mingyan LUO
1
;
Meizong CHEN
;
Imshik LEE
Author Information
1. College of Physics, Nankai University, Tianjin 300071, China.
- Publication Type:Journal Article
- MeSH:
Amino Acid Sequence;
Drug Design;
Humans;
Models, Molecular;
Oligopeptides;
chemistry;
Platelet Aggregation Inhibitors;
chemical synthesis;
chemistry;
Platelet Glycoprotein GPIIb-IIIa Complex;
antagonists & inhibitors;
chemistry
- From:
Chinese Journal of Biotechnology
2008;24(2):297-301
- CountryChina
- Language:Chinese
-
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.
