Computational Discovery of Angiotensin-(1-7)-like Peptides Targeting the MAS Receptor from the Genomic Dark Matter of Saccharomyces cerevisiae

Figures

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  Figure 1. Structural comparison of Ang-(1-7) and intergenic-region-derived peptides from Saccharomyces cerevisiae. (A) Three-dimensional structure of Ang-(1-7). (B-C) Predicted three-dimensional structures of dark peptide 1 and dark peptide 2 generated using I-TASSER. (D-E) Structural superimposition of Ang-(1-7) with dark peptide 1 and dark peptide 2, respectively, showing close conformational overlap. The calculated RMSD values were 1.67 Å for dark peptide 1 and 1.78 Å for dark peptide 2 relative to Ang-(1-7), indicating structural similarity to the native peptide ligand.

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  Figure 2. Predicted structure and ligand-binding pocket of the human MAS receptor. (A) Ribbon representation of the modeled MAS receptor showing the characteristic seven-transmembrane helical architecture of a class A GPCR. (B) Surface representation of the predicted extracellular ligand-binding pocket identified using SiteMap. (C) Key residues forming the putative Ang-(1-7)-binding region of the MAS receptor.

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  Figure 3. Docking poses and interaction profiles of Ang-(1-7) and intergenic-region-derived peptides bound to the MAS receptor. (A) Docked pose of Ang-(1-7) within the predicted MAS receptor binding pocket. (B) Two-dimensional interaction diagram of the Ang-(1-7)-MAS receptor complex. (C) Docked pose of dark peptide 1 within the MAS receptor binding pocket. (D) Two-dimensional interaction diagram of the dark peptide 1-MAS receptor complex. (E) Docked pose of dark peptide 2 within the MAS receptor binding pocket. (F) Two-dimensional interaction diagram of the dark peptide 2-MAS receptor complex. Interaction legend: Green = hydrogen bond; light green = carbon hydrogen bond; orange = salt-bridge/charge interaction; pink = π-π or π-alkyl interaction; purple = alkyl contact; yellow = π-sulfur interaction

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  Figure 4. Molecular dynamics simulation analysis of MAS receptor complexes. (A) Root mean square deviation (RMSD) profiles showing the overall structural stability of the MAS receptor complexes during 100 ns simulations. (B) Root mean square fluctuation (RMSF) profiles showing residue-level flexibility. (C) Radius of gyration (Rg) analysis showing compactness of the receptor-peptide complexes. (D) Hydrogen-bond analysis showing the stability of receptor-ligand interactions during simulation. Different colors of peak in the graph are as follows Ang-(1-7)-Black, dark peptide 1- Red, dark peptide 2 - Green.