Atomistic Molecular Insights into Angiotensin-(1-7) Interpeptide Interactions

Angiotensin-(1-7) is an endogenous peptide known forits vasoprotective,antioxidant, and anti-inflammatory effects, making it a promisingtherapeutic candidate for various clinical conditions. However, thepeptide exhibits pH-dependent physical instability in aqueous solutions,and a comprehensive atomistic study elucidating this behavior andits implications is currently lacking. Therefore, we performed all-atommolecular dynamics simulations to investigate the early formationof angiotensin-(1-7) oligomeric aggregates under different conditions:acidic and neutral pH-like conditions, physiological and high ionicstrength, and high and low peptide concentrations. Our results areas follows: (1) under acidic pH-like conditions, angiotensin-(1-7)showed minimal clustering, (2) under neutral pH-like conditions, thepeptides aggregated into a single cluster, consistent with the reportedphysical instability, and (3) increasing salt concentration underacidic pH-like conditions resulted in aggregation similar to thatobserved under neutral pH-like conditions. These results suggest thata combination of salt concentration and pH conditions can modulateangiotensin-(1-7) aggregation. Our protocol (molecular dynamics +cluster analysis + amino acid interaction map analysis) is generaland could be applied to other peptides to study interpeptide interactionmechanisms.