Computational modeling of cyclotides as antimicrobial agents against Neisseria gonorrhoeae PorB porin protein: integration of docking, immune, and molecular dynamics simulations.
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Abstract
Background: Neisseria gonorrhoeae is the bacterium responsible for gonorrhoea, one of the most common sexually transmitted infections (STIs) globally. In 2020, the World Health Organization (WHO) estimated 82.4 million new cases of Neisseria gonorrhoeae infections. Current treatments rely on antibiotics, but the emergence of multi drug resistance (MDR) strains poses a significant threat to public health. This research aims to use computational modeling of cyclotides as antimicrobial agents targeting the Neisseria gonorrhoeae PorB Porin protein to inhibit its pathogenicity.
Methodology: The PorB Porin protein was retrieved from the Protein Data Bank (PDB ID: 4AUI), cleaned, and visualized using Discovery Visual Studio. Physicochemical properties were predicted using ProtParam. Cyclotides were obtained from the CyBase database, with 3D models generated and refined via the Swiss Model for docking studies. HDOCK was used for molecular docking. Toxicity and allergenicity predictions were performed with ToxinPred and AlgPred. A heatmap of the peptide was created using Protein-Sol. Molecular dynamics (MD) simulations were conducted for 100,000 picoseconds using Desmond from Schrödinger LLC, while binding energy was analyzed using MMGBSA. Immune response simulations were done with C-ImmSim 10.1, and peptide simulation in water was performed via WebGro.
Results: The protein's GRAVY value is -0.539, indicating moderate hydrophilicity, and its isoelectric point is 9.14, suggesting a fundamental nature. Globa D had the highest docking score (-270.04 kcal/mol) and was deemed non-toxic and non-allergenic. MD simulations showed stable protein-ligand interactions, and MMGBSA revealed a low binding energy of -36.737 kcal/mol. Immune simulations indicated an effective immune response and peptide simulations demonstrated Globa D's stability in water, making it a potential candidate for pharmaceutical applications.
Conclusion: Globa D proved the best drug candidate against Neisseria gonorrhoeae by inhibiting PorB Porin protein chain A. Further in vitro and in vivo studies are recommended to validate these findings and explore clinical applications.
期刊介绍：
Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide.
Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”.
All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.
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