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

Angiotensin-(1-7) is an endogenous peptide known for its vasoprotective, antioxidant, and anti-inflammatory effects, making it a promising therapeutic candidate for various clinical conditions. However, the peptide exhibits pH-dependent physical instability in aqueous solutions, and a comprehensive atomistic study elucidating this behavior and its implications is currently lacking. Therefore, we performed all-atom molecular dynamics simulations to investigate the early formation of angiotensin-(1-7) oligomeric aggregates under different conditions: acidic and neutral pH-like conditions, physiological and high ionic strength, and high and low peptide concentrations. Our results are as follows: (1) under acidic pH-like conditions, angiotensin-(1-7) showed minimal clustering, (2) under neutral pH-like conditions, the peptides aggregated into a single cluster, consistent with the reported physical instability, and (3) increasing salt concentration under acidic pH-like conditions resulted in aggregation similar to that observed under neutral pH-like conditions. These results suggest that a combination of salt concentration and pH conditions can modulate angiotensin-(1-7) aggregation. Our protocol (molecular dynamics + cluster analysis + amino acid interaction map analysis) is general and could be applied to other peptides to study interpeptide interaction mechanisms.

Molecular Docking and Dynamics Simulation of Protein ß-Tubulin and Antifungal Cyclic Lipopeptides.

To elucidate interactions between the antifungal cyclic lipopeptides iturin A, fengycin, and surfactin produced by Bacillus bacteria and the microtubular protein ß-tubulin in plant pathogenic fungi (Fusarium oxysporum, Colletrotrichum gloeosporioides, Alternaria alternata, and Fusarium solani) in molecular docking and molecular dynamics simulations, we retrieved the structure of tubulin co-crystallized with taxol from the Protein Data Bank (PDB) (ID: 1JFF) and the structure of the cyclic lipopeptides from PubChem (Compound CID: 102287549, 100977820, 10129764). Similarity and homology analyses of the retrieved ß-tubulin structure with those of the fungi showed that the conserved domains shared 84% similarity, and the root mean square deviation (RMSD) was less than 2 Å. In the molecular docking studies, within the binding pocket, residues Pro274, Thr276, and Glu27 of ß-tubulin were responsible for the interaction with the cyclic lipopeptides. In the molecular dynamics analysis, two groups of ligands were formed based on the number of poses analyzed with respect to the RMSD. Group 1 was made up of 10, 100, and 500 poses with distances 0.080 to 0.092 nm and RMSDs of 0.10 to 0.15 nm. For group 2, consisting of 1000 poses, the initial and final distance was 0.1 nm and the RMSDs were in the range of 0.10 to 0.30 nm. These results suggest that iturin A and fengycin bind with higher affinity than surfactin to ß-tubulin. These two lipopeptides may be used as lead compounds to develop new antifungal agents or employed directly as biorational products to control plant pathogenic fungi.