Molecular Docking and Structure-Activity Relationship Analysis of Target Compounds against Glyceraldehyde-3-Phosphate Dehydrogenase in Azithromycin-Resistant Neisseria gonorrhoeae

Abstract

The emergence of drug-resistant strains of Neisseria gonorrhoeae poses a significant global health challenge, necessitating the development of novel antimicrobial agents. This study focuses on the potential of phenolic compounds to target the enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in N. gonorrhoeae, a key protein involved in glycolysis and implicated in various pathological mechanisms. Among the compounds evaluated, quercetin demonstrated significant binding affinity to N. gonorrhoeae-derived GAPDH. Structural integrity assessments using Procheck software and molecular docking simulations confirmed the binding capacity of quercetin. Molecular dynamics simulations further explored the stability and flexibility of the quercetin-N. gonorrhoeae GAPDH complex. The results revealed interactions between quercetin and specific amino acid residues, suggesting potential binding sites crucial for antimicrobial action. This information provides valuable insights into the development of quercetin-based therapeutics targeting drug-resistant N. gonorrhoeae, addressing the urgent need for novel antimicrobial agents.