In Silico Assessment of Amino Acid–Protein Interactions in Coronary Artery Disease: Molecular Insights for Functional Biology

Abstract

This study aimed to evaluate the molecular-level interactions between six Coronary artery disease (CAD)-associated amino acids (L-arginine, L-cystine, L-asparagine, L-isoleucine, L-leucine, and trans-4-hydroxyproline) and four cardiovascular target proteins (Angiotensin-converting enzyme (ACE)–1O86, Endothelial nitric oxide synthase (eNOS)–3NOS, β₁-adrenergic receptor (β₁-AR)–2VT4, and Transient Receptor Potential Vanilloid 2 (TRPV2)–8FFM). Ligands were prepared using Schrödinger LigPrep, and proteins were optimized with the Protein Preparation Wizard. Molecular docking simulations were conducted using the Glide SP and XP algorithms. Binding affinities were calculated using GlideScore. Hydrogen bonds, ionic interactions, metal coordination, and π–alkyl contacts were analyzed via Maestro visualization software. L-cystine exhibited high binding affinity with all target proteins, showing particularly strong interactions with ACE (−10.663 kcal/mol) and eNOS (−6.735 kcal/mol). Trans-4-hydroxyproline also displayed favorable binding, supported by extensive hydrogen bonding and zinc coordination. In contrast, hydrophobic amino acids such as L-isoleucine and L-leucine showed weaker interactions. ACE presented the most favorable binding environment for the selected ligands. The strong binding affinities of L-cystine and trans-4-hydroxyproline, particularly to ACE and eNOS, suggest their potential as candidate inhibitors. These effects may be attributed to disulfide bridge formation and hydrogen bond capacity, respectively, which contribute to enhanced binding stability. L-cystine and trans-4-hydroxyproline emerge as promising inhibitor candidates for key cardiovascular proteins implicated in CAD. These findings underscore the potential of amino acid–based therapeutic modulation and provide valuable insight for rational drug design and biomarker development in cardiovascular disease.

Keywords

• Amino acid–protein interaction
• Molecular docking
• Cardiovascular molecular targets
• In silico analysis

Ethical Statement

Ethics committee approval was not obtained as no studies on animals or humans were conducted in this study.

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