Proteomic information revealed approximately 3,923 proteins in Mycobacterium tuberculosis H₃₇Rv genome of which around ∼25% of proteins are hypothetical proteins (HPs). The present work comprises computational approaches to identify and characterize the HPs of M. tuberculosis that symbolize the putative target for rationale development of a drug or antituberculosis strategy. Proteins were primarily classified based on motif and domain information, which were further analyzed for the presence of virulence factors (VFs), determination of localization, and signal peptide/enzymatic cleavage sites. 863 HPs were found, and 599 HPs were finalized based on motifs, that is, GTP (525), Trx (47), SAM (14), PE-PGRS (5), and CBD (8). 80 HPs contain virulence factor (VF), 24 HPs localized in membrane region, and 4 HPs contain signal peptide/enzymatic cleavage sites. The overall parametric study finalizes four HPs Rv0679c, Rv0906, Rv3627c, and Rv3811 that also comprise GTPase domain. Structure prediction, structure-based function prediction, molecular docking and mutation analysis of selected proteins were done. Docking studies revealed that GTP and GTPase inhibitor (mac0182344) were docked with all four proteins with high affinities. In silico point mutation studies showed that substitution of aspartate with glycine within a GTPase motif showed the largest decrease in stability and pH differentiation also affects protein's stability. This analysis thus fixes a roadmap in the direction of finding potential target of this bacterium for drug development and enlightens the efficacy of GTP as a major regulator of Mycobacterial cellular pathways.

中文翻译：

---

结核分枝杆菌 H37Rv 假设蛋白的领域分化：发现细菌存活潜力的路线图

蛋白质组学信息揭示了结核分枝杆菌H ₃₇ Rv 基因组中大约 3,923 种蛋白质，其中约 25% 的蛋白质是假设蛋白质 (HP)。目前的工作包括识别和表征结核分枝杆菌HPs 的计算方法这象征着合理开发药物或抗结核策略的假定目标。主要根据基序和结构域信息对蛋白质进行分类，进一步分析毒力因子 (VF) 的存在、定位的确定和信号肽/酶切割位点。共找到 863 个 HP，根据基序最终确定了 599 个 HP，即 GTP (525)、Trx (47)、SAM (14)、PE-PGRS (5) 和 CBD (8)。80 个 HPs 含有毒力因子 (VF)，24 个 HPs 位于膜区域，4 个 HPs 含有信号肽/酶切位点。整体参数研究最终确定了四个 HP Rv0679c、Rv0906、Rv3627c 和 Rv3811，它们也包含 GTPase 结构域。对选定的蛋白质进行结构预测、基于结构的功能预测、分子对接和突变分析。计算机点突变研究表明，在 GTPase 基序内用甘氨酸取代天冬氨酸显示出稳定性的最大下降，并且 pH 分化也影响蛋白质的稳定性。因此，该分析确定了寻找该细菌用于药物开发的潜在靶标的路线图，并启发了 GTP 作为分枝杆菌细胞途径主要调节剂的功效。