PDF(Pubmed)
Abstract：
Multiple drug-resistant fungal species are associated with the development of diseases. Thus, more efficient drugs for the treatment of these aetiological agents are needed. Rondonin is a peptide isolated from the haemolymph of the spider Acanthoscurria rondoniae. Previous studies have shown that this peptide has antifungal activity against Candida sp. and Trichosporon sp. strains, acting on their genetic material. However, the molecular targets involved in its biological activity have not yet been described. Bioinformatics tools were used to determine the possible targets involved in the biological activity of Rondonin. The PharmMapper server was used to search for microorganismal targets of Rondonin. The PatchDock server was used to perform the molecular docking. UCSF Chimera software was used to evaluate these intermolecular interactions. In addition, the I-TASSER server was used to predict the target ligand sites. Then, these predictions were contrasted with the sites previously described in the literature. Molecular dynamics simulations were conducted for two promising complexes identified from the docking analysis. Rondonin demonstrated consistency with the ligand sites of the following targets: outer membrane proteins F (id: 1MPF) and A (id: 1QJP), which are responsible for facilitating the passage of small molecules through the plasma membrane; the subunit of the flavoprotein fumarate reductase (id: 1D4E), which is involved in the metabolism of nitrogenous bases; and the ATP-dependent Holliday DNA helicase junction (id: 1IN4), which is associated with histone proteins that package genetic material. Additionally, the molecular dynamics results indicated the stability of the interaction of Rondonin with 1MPF and 1IN4 during a 10 ns simulation. These interactions corroborate with previous in vitro studies on Rondonin, which acts on fungal genetic material without causing plasma membrane rupture. Therefore, the bioprospecting methods used in this research were considered satisfactory since they were consistent with previous results obtained via in vitro experimentation.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00224-1.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00224-1.
摘要：
多种耐药真菌物种与疾病的发展有关。因此，需要更有效的药物来治疗这些病原体。Rondonin是从蜘蛛棘刺的血淋巴中分离的肽。先前的研究表明，该肽对念珠菌具有抗真菌活性。和Trichosporonsp.菌株，作用于他们的遗传物质。然而,涉及其生物活性的分子靶标尚未被描述。使用生物信息学工具来确定参与Rondonin生物活性的可能靶标。PharmMapper服务器用于搜索Rondonin的微生物目标。PatchDock服务器用于执行分子对接。使用UCSFChimera软件评估这些分子间相互作用。此外,I-TASSER服务器用于预测靶配体位点。然后，这些预测与文献中先前描述的网站形成对比.对从对接分析中鉴定出的两种有希望的复合物进行了分子动力学模拟。Rondonin证明与以下靶标的配体位点一致：外膜蛋白F（id：1MPF）和A（id：1QJP），负责促进小分子通过质膜;黄素蛋白富马酸还原酶的亚基（id：1D4E），参与含氮碱基的代谢;和ATP依赖性霍利迪DNA解旋酶连接（id：1IN4），与包装遗传物质的组蛋白相关。此外,分子动力学结果表明，在10ns的模拟过程中，Rondonin与1MPF和1IN4相互作用的稳定性。这些相互作用证实了先前对Rondonin的体外研究，它作用于真菌遗传物质而不会引起质膜破裂。因此,这项研究中使用的生物勘探方法被认为是令人满意的，因为它们与以前通过体外实验获得的结果一致。
■在线版本包含补充材料，可在10.1007/s40203-024-00224-1获得。
■在线版本包含补充材料，可在10.1007/s40203-024-00224-1获得。
