高亲和力益生菌肽抑制PAK1胃癌蛋白的模拟研究:比较方法

IF 2.6 4区 生物学 Q2 BIOLOGY
Humera Azad , Muhammad Yasir Akbar , Jawad Sarfraz , Waseem Haider , Shakira Ghazanfar
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引用次数: 0

摘要

胃肠道(GI)癌症的高死亡率是对世界健康的一个主要威胁,特别是在亚洲、南美洲和欧洲。由于胃肠道(GI)癌症的复杂性和异质性,使得开发有效的治疗方法变得困难,因此需要新的方法。为了研究针对P21活化激酶1 (PAK1)的肽基疗法在胃肠道癌症中的潜力,我们使用DBsORF数据库来预测两种细菌菌株(植物乳杆菌和戊糖Pediococcus pentosaeus)基因组中的肽。在使用Swiss Model工具对这些肽的三维(3D)结构进行建模后,将能量最小化应用于稳定性。ToxinPred用于毒性分析,以验证鉴定的肽的安全性。目标蛋白PAK1的三维结构从蛋白质数据库(PDB)中取出,准备进行计算机分析。为了确定每个菌株中具有良好PAK1结合特性的最佳肽,使用ClusPro服务器进行分子对接分析。plantarum和P. pentosaceus的肽库不同,一些候选候选具有低毒性;例如,P. pentosaceus的VOIOYA_1513和L. plantarum的BVNTGZ_2921与PAK1具有较高的结合能和稳定的相互作用。一旦对结合能、氢键和非键接触进行了评估,就可以选择有希望的候选肽。了解肽- pak1复合物的动力学是通过格罗宁根分子模拟机(Gromacs)进行的分子动力学模拟来实现的。轨迹分析测量,如旋转半径(Rg)、均方根偏差(RMSD)和均方根波动(RMSF),提供了在100 ns模拟过程中对结构稳定性和波动的洞察。分子动力学模拟验证了这些复合物的稳定性,这表明,经过进一步的实验验证,它们可能是有希望的治疗候选者。未来的研究项目和药物开发计划将受益于详细的计算方法,它提供了针对胃肠道癌症中PAK1的肽类治疗的设计和评估信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Simulation studies to identify high-affinity probiotic peptides for inhibiting PAK1 gastric cancer protein: A comparative approach
A major threat to world health is the high death rate from gastrointestinal (GI) cancer, especially in Asia, South America, and Europe. The new approaches are needed because of the complexity and heterogeneity of gastrointestinal (GI) cancer, which has made the development of effective treatments difficult. To investigate the potential of peptide-based therapies that target the P21 Activated Kinase 1 (PAK1) in GI cancer, we are using the DBsORF database to predict peptides from the genomes of two bacterial strains: Lactobacillus plantarum and Pediococcus pentosaceus. Energy minimization is then applied for stability after the three-dimensional (3D) structures of these peptides are modeled using the Swiss Model tool. ToxinPred is used for toxicity analysis to verify the safety profiles of the identified peptides. The three-dimensional structure of the target protein PAK1 is taken out of the Protein Data Bank (PDB) and ready for computer analyses. To identify the top-performing peptides for each strain that have good PAK1 binding properties, molecular docking analysis is performed using the ClusPro server. The peptide repertoires of L.plantarum and P. pentosaceus are distinct, and some candidates display low toxicity; for instance, VOIOYA_1513 from P. pentosaceus and BVNTGZ_2921 from L. plantarum demonstrate high binding energies and stable interactions with PAK1. Once the binding energies, hydrogen bonds, and non-bonded contacts have been evaluated, promising peptide candidates are selected. Understanding the dynamics of the peptide-PAK1 complexes is achieved through molecular dynamics simulations performed with the Groningen machine for molecular simulation (Gromacs). Trajectory analysis measures like Radius of Gyration (Rg), Root Mean Square Deviation (RMSD), and Root Mean Square Fluctuation (RMSF) provide insight into the stability and fluctuations of the structure during a 100 ns simulation. Molecular dynamics simulations validate the stability of these complexes, suggesting that, subject to further experimental validation, they could be promising therapeutic candidates. Future research projects and drug development initiatives will benefit from the detailed computational approach, which offers information about the design and evaluation of peptide-based treatments that target PAK1 in GI cancer.
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来源期刊
Computational Biology and Chemistry
Computational Biology and Chemistry 生物-计算机:跨学科应用
CiteScore
6.10
自引率
3.20%
发文量
142
审稿时长
24 days
期刊介绍: Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.
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