脆弱拟杆菌是一种革兰氏阴性、专性厌氧细菌，是正常肠道微生物群的一员，在正常情况下，特别是在胃肠道或胃肠道中，促进人体发挥许多重要作用。有时，由于遗传、表观遗传学和环境因素，脆弱拟杆菌及其蛋白质开始与肠上皮相互作用，从而破坏内壁，导致结直肠癌 (CRC)。为了识别这些蛋白质，我们在研究中采用了一种新颖的消减蛋白质组学方法。金属蛋白酶 II (MPII) 是一种脆弱拟杆菌毒素 (bft)，对其毒力和独特途径进行了研究，以证明其致病性的特异性和独特性，然后与一组类似药物的天然小分子进行分子对接，以发现针对该毒素的潜在抑制剂。毒素。对所有这些已识别的抑制剂样分子进行了 ADMET 计算和详细的理化特性分析，以预测其成药性、胃肠道吸收、血脑屏障和皮肤渗透性等。结果，总共获得了十种具有最小结合能的化合物，并进行了蛋白质-化合物相互作用分析。相互作用分析显示 MPII 中最常见的配体相互作用残基是 His 345、Glu 346、His 339、Gly 310、Tyr 341、Pro 340、Asp 187、Phe 309、Lys 307、Ile 185、Thr 308 和 Pro 184。因此，选择与 MPII 复合的具有最佳结合能的前三种化合物来分析它们的轨迹。 RMSD、RMSF、Rg 和 MMPBSA 分析表明，除了作为 MPII 潜在抑制剂的所有特性和品质外，所有化合物都表现出良好的结合力，并在整个模拟时间内保持复合物稳定和紧凑。© 2024 由 Elsevier Ltd 出版。

Bacteroides fragilis, a gram negative and obligate anaerobe bacterium, is a member of normal gut microbiota and facilitates many essential roles being performed in human body in normal circumstances specifically in Gastrointestinal or GI tract. Sometimes, due to genetics, epigenetics, and environmental factors, Bacteroides fragilis and their protein(s) start interacting with intestinal epithelium thus damaging the lining leading to colorectal cancers (CRC). To identify these protein(s), we incorporated a novel subtractive proteomics approach in the study. Metalloproteinase II (MPII), a Bacteroides fragilis toxin (bft), was investigated for its virulence and unique pathways to demonstrate its specificity and uniqueness in pathogenicity followed by molecular docking against a set of small drug-like natural molecules to discover potential inhibitors against the toxin. All these identified inhibitor-like molecules were analyzed for their ADMET calculations and detailed physiochemical properties to predict their druggability, GI absorption, blood brain barrier and skin permeation, and others. Resultantly, a total of ten compounds with the least binding energies were obtained and were subjected to protein-compound interaction analysis. Interaction analysis revealed the most common ligand-interacting residues in MPII are His 345, Glu 346, His 339, Gly 310, Tyr 341, Pro 340, Asp 187, Phe 309, Lys 307, Ile 185, Thr 308, and Pro 184. Therefore, top three compounds complexed with MPII having best binding energies were selected in order to analyze their trajectories. RMSD, RMSF, Rg and MMPBSA analysis revealed that all compounds showed good binding and keeping the complex stable and compact throughout the simulation time in addition to all properties and qualities of being a potential inhibitor against MPII.© 2024 Published by Elsevier Ltd.