The investigation into the effect of the length of RGD peptides and temperature on the interaction with the αIIbβ۳ integrin: a molecular dynamic study

The tripeptide Arg-Gly-Asp acid (RGD) is a protein sequence in the binding of proteins to cell surfaces, and is involved in various biological processes such as cell adhesion to the extracellular matrix, platelet activation, hemostasis, etc. The C۲ domain of the Von Willebrand Factor (VWF), containing the RGD motif, plays an important role in the initial homeostasis process. It binds to the αIIbβ۳ integrin and stimulates platelet aggregation. We have investigated, using the Molecular Dynamic (MD) simulation method, the effect of the RGD-peptide length, and temperature variation, on the binding to the αIIbβ۳ integrin receptor. We examined ۱۰ different structural modes of the αIIbβ۳ at three different temperatures; ۲۳۷K, ۳۱۰K and ۳۱۸K. Our findings show that the amino acids that form a binding pocket include Asp۲۲۴, Tyr۲۳۴, Ser۲۲۶, Tyr۱۹۰, Tyr۱۸۹, Trp۲۶۰, Trp۲۶۲, Asp۲۵۹, Lys۲۵۳, Arg۲۱۴, Asp۲۱۷, Ser۱۶۱ and Ala۲۱۸ and that the ligand-receptor interaction was increased at higher temperatures. It was also found that the increase in the number of ligands’ amino acids and their types (% glycine) plays an important role in the stability, conformation, and ligand-receptor interaction.

Keywords:

Molecular Dynamic , RGD containing peptides , αIIbβ۳ integrin , Active site , Von Willebrand Factor