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ORIGINAL RESEARCH article

Front. Chem.
Sec. Theoretical and Computational Chemistry
Volume 12 - 2024 | doi: 10.3389/fchem.2024.1493165
This article is part of the Research Topic Natural and Artificially-Engineered Medicines: Design, Characterization and Diseases Management View all 4 articles

Computational Modeling of Cyclotides as Antimicrobial Agents Against Neisseria gonorrhoeae PorB Porin Protein: Integration of Docking, Immune, and Molecular Dynamics Simulations

Provisionally accepted
Muzamal Hussain Muzamal Hussain 1Nazia Kanwal Nazia Kanwal 1*Alishba Jahangir Alishba Jahangir 1*Nouman Ali Nouman Ali 2*Nimra Hanif Nimra Hanif 2*Obaid Ullah Obaid Ullah 3*
  • 1 Superior University, Lahore, Punjab, Pakistan
  • 2 University of Central Punjab, Lahore, Pakistan
  • 3 University of Agriculture, Faisalabad, Faisalabad, Punjab, Pakistan

The final, formatted version of the article will be published soon.

    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 resistant (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.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.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 proteinligand 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.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.

    Keywords: Neisseria gonorrhoeae, Porb Porin, Cyclotide, Multi drug resistant (MDR), antibiotic resistance, Insilico

    Received: 11 Sep 2024; Accepted: 06 Nov 2024.

    Copyright: © 2024 Hussain, Kanwal, Jahangir, Ali, Hanif and Ullah. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Nazia Kanwal, Superior University, Lahore, 54000, Punjab, Pakistan
    Alishba Jahangir, Superior University, Lahore, 54000, Punjab, Pakistan
    Nouman Ali, University of Central Punjab, Lahore, Pakistan
    Nimra Hanif, University of Central Punjab, Lahore, Pakistan
    Obaid Ullah, University of Agriculture, Faisalabad, Faisalabad, 38000, Punjab, Pakistan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.