Laminin-Derived Peptides Bind Neuropilin-1 at the VEGF-A165 Binding Pocket

Laminin-derived peptide Ac-Tyr-Ile-Gly-Ser-Arg-NH2 binds the canonical VEGF-A165 pocket of b1-NRP-1 with the highest mean equilibrated occupancy (60.3 ± 34.6%) in simulations.

• Why it matters: NRP-1’s VEGF-A165 binding site is linked to glioblastoma progression, but it was unclear whether laminin-derived peptide fragments can associate with this pocket.
• What they did: AlphaFold 3 complex prediction was followed by 15 s all-atom molecular dynamics, pocket-occupancy and interaction analyses, and FoldX scoring to compare peptide 1 with retro and retro-inverso analogs.
• The result: NanoDSF with recombinant NRP-1 and synthetic peptides gave low micromolar apparent dissociation constants (12.7 M–33.3 M), supporting predicted pocket interactions and suggesting peptide analogs for further optimization.

AI summary of the abstract · may contain errors · not medical advice · read the paper.