Molecular basis for the targeted binding of RGD-containing peptide to integrin αVβ3

Integrin αVβ3-targeting peptides with an exposed arginine-glycine-aspartate (RGD) sequence play a crucial role in targeted anticancer drug delivery. The effects of RGD-containing peptide structure and quantity on mechanism of targeted binding of RGD-containing peptide to integrin αVβ3 were studied intensively at the molecular level via molecular dynamic simulations. Targeted recognization was mainly driven by the electrostatic interactions between the residues in RGD and the metal ions in integrin αVβ3, and cyclic arginine-glycine-aspartate-phenylalanine-valine (RGDFV) peptide appeared to be a better vector than the linear RGD-containing peptides. In addition, the optimal molar concentration ratio of RGD peptides to integrin αVβ3 appeared to be 2:1. These results will help improve the current understanding on the mechanism of interactions between RGD and integrin αVβ3, and promote the application prospects of RGD-based vectors in tumor imaging, diagnosis, and cancer therapy.