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

Area of Science:

• Biochemistry
• Physical Chemistry
• Pharmacology

Background:

• Angiotensin-(1-7) possesses significant vasoprotective, antioxidant, and anti-inflammatory properties.
• Its therapeutic potential is hindered by pH-dependent physical instability in aqueous solutions.
• A detailed atomistic understanding of this instability is lacking.

Purpose of the Study:

• To investigate the aggregation behavior of angiotensin-(1-7) using all-atom molecular dynamics simulations.
• To elucidate the impact of pH, ionic strength, and peptide concentration on angiotensin-(1-7) oligomerization.
• To provide insights into the mechanisms underlying peptide physical instability.

Main Methods:

• All-atom molecular dynamics simulations were employed.
• Simulations were conducted under varying conditions: acidic and neutral pH, physiological and high ionic strength, and varying peptide concentrations.
• Cluster analysis and amino acid interaction map analysis were utilized to interpret results.

Main Results:

• Angiotensin-(1-7) exhibited minimal clustering under acidic pH conditions.
• Aggregation into a single cluster was observed under neutral pH conditions, correlating with reported instability.
• Increased salt concentration under acidic pH induced aggregation similar to neutral pH conditions.

Conclusions:

• Peptide aggregation of angiotensin-(1-7) is modulated by a combination of pH and salt concentration.
• The findings offer a mechanistic basis for understanding and potentially mitigating angiotensin-(1-7) instability.
• The employed computational protocol is applicable to studying interpeptide interactions in other systems.