Atomistic molecular insight on Angiotensin-(1-7) inter-peptide interactions
Angiotensin-(1-7) is an endogenous peptide with vaso-protective, anti-oxidant, and anti-inflammatory effects which has been proposed as a potential therapeutic agent in a wide range of clinical conditions. Angiotensin-(1-7) presents a pH-dependent physical instability in aqueous solutions; however, it still lacks a proper atomistic study that provides insights into this behavior and its potential implications. Hence, we studied the formation of early Angiotensin-(1-7) oligomeric aggregates in an aqueous environment under acidic and neutral conditions; physiological and high ionic strength; and high and low peptide concentrations using all-atom Molecular Dynamics simulations. Our main findings are: 1) at acidic pH, there is a poor level of Angiotensin-(1-7) clustering, while, 2) at neutral pH, peptides aggregate in a unique cluster, in good trend with experimental physical instability reports and 3) an increase in salt concentration at acidic pH gives place to aggregation similar to the case at neutral pH. Our results open the route for the modulation of Angiotensin-(1-7) aggregation through a combination of salt concentration and pH conditions. Our protocol (MD + cluster analysis + amino acids interaction map analysis) is general and could be applied to other peptides to study the inter-peptide interaction mechanisms.