LAUSR

Peptides with an exposed arginine–glycine–aspartate (Arg–Gly–Asp, RGD) sequence targeting the integrin αVβ3 play an important role in targeted anticancer drug delivery. The interaction of multiple RGD‐containing peptides and two αVβ3 molecules was studied via MD simulation. Results revealed that not all six RGD‐containing peptides interact with αVβ3 and interaction strengths differed among the peptides. The specific identification sites included the guanidine group of the ARG residue in the RGD peptide and the carboxyl group of the ASP residue in integrin αVβ3. Therefore, formation of a salt bridge between ARGRGD and the ASP residue was the main mechanism of interaction. H‐bonds also played an important role in the observed interaction. The interaction between RGD‐containing peptides and αVβ3 was influenced by two factors: the relative orientation and distance between these groups. The RGD cluster, which could markedly increase the number of absorbed RGD monomers and enhance the cellular uptake of nano‐medicines, was observed in this system.