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BACKGROUND

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 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 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 by inhibiting PorB Porin protein chain A. Further and studies are recommended to validate these findings and explore clinical applications.

BACKGROUND

METHODOLOGY

RESULTS

CONCLUSION

Globa D proved the best drug candidate against by inhibiting PorB Porin protein chain A. Further and studies are recommended to validate these findings and explore clinical applications.

背景

淋病奈瑟菌是导致淋病的细菌，淋病是全球最常见的性传播感染（STIs）之一。2020年，世界卫生组织（WHO）估计有8240万例新的淋病奈瑟菌感染病例。目前的治疗依赖抗生素，但多重耐药（MDR）菌株的出现对公共卫生构成了重大威胁。本研究旨在利用环肽的计算模型作为针对淋病奈瑟菌孔蛋白PorB的抗菌剂，以抑制其致病性。

方法

从蛋白质数据库（PDB ID：4AUI）中检索淋病奈瑟菌孔蛋白PorB，进行清理，并使用Discovery Visual Studio进行可视化。使用ProtParam预测其理化性质。从CyBase数据库中获取环肽，并通过瑞士模型生成和优化3D模型以进行对接研究。使用HDOCK进行分子对接。用ToxinPred和AlgPred进行毒性和致敏性预测。使用Protein-Sol创建肽的热图。使用Schrödinger LLC公司的Desmond进行100000皮秒的分子动力学（MD）模拟，同时使用MMGBSA分析结合能。用C-ImmSim 10.1进行免疫反应模拟，并通过WebGro在水中进行肽模拟。

结果

该蛋白的亲水性总平均值（GRAVY）值为-0.539，表明具有中等亲水性，其等电点为9.14，显示出碱性性质。Globa D具有最高的对接分数（-270.04 kcal/mol），且被认为无毒且无致敏性。MD模拟显示蛋白质-配体相互作用稳定，MMGBSA显示结合能低至-36.737 kcal/mol。免疫模拟表明有有效的免疫反应且肽模拟证明Globa D在水中稳定，使其成为药物应用的潜在候选物。