Centre for Bioinformatics, Kamalnayan Bajaj Institute for Research in Vision and Ophthalmology, Vision Research Foundation, Chennai, India.
J Biomol Struct Dyn. 2020 Jul;38(11):3131-3143. doi: 10.1080/07391102.2019.1652691. Epub 2019 Aug 12.
() is a major causative of infectious blindness in world. It is a real challenge to combat infection as it is an intracellular pathogen. Hence, it is essential to determine the most potential targets of in order to inhibit or suppress its virulence during its infectious phase. Thus, in this study, the highly expressed-cum-most essential genes reported through our earlier study were reprioritized by structure-based comparative binding site analysis with host proteome. Therefore, computational approaches involving molecular modelling, large-scale binding site prediction and comparison, molecular dynamics simulation studies were performed to narrow down the most potential targets. Furthermore, high-throughput virtual screening and ADMETox were also performed to identify potential hits that shall efficiently inhibit the prioritised targets. Hence, by this study we report Pyruvoyl-dependent arginine decarboxylase (PvlArgDC), DNA-repair protein (RecO) and porin (outer membrane protein) as the most viable targets of which can be potentially targeted by compounds, NSC_13086, MFCD00276409, MFCD05662003, respectively. AbbreviationsChlamydia trachomatisSTDSexually transmitted diseaseHTVSHigh-throughput virtual screeningADMEToxAbsorption, Distribution, Metabolism, Excretion and ToxicityPMPocketMatchMDMolecular Dynamics simulationSPStandard precisionXPExtra precisionMMGBSAMolecular mechanics energies combined with generalised Born and surface area continuum solvationOMPOuter membrane proteinPvlArgDCPyruvoyl-dependent arginine decarboxylaseRecORecombination protein O.Communicated by Ramaswamy H. Sarma.
沙眼衣原体是世界范围内导致感染性盲的主要原因。由于是胞内病原体，因此对抗感染是一个真正的挑战。因此，确定沙眼衣原体在感染期最具潜力的靶标对于抑制或抑制其毒力至关重要。因此，在这项研究中，通过与宿主蛋白质组的结构比较结合位点分析，重新优先考虑了我们之前的研究中报道的高表达和最基本的基因。因此，进行了涉及分子建模、大规模结合位点预测和比较、分子动力学模拟研究的计算方法，以缩小最具潜力的靶标范围。此外，还进行了高通量虚拟筛选和 ADMETox，以识别能够有效抑制优先靶标的潜在命中。因此，通过这项研究，我们报告了依赖于丙酮酸的精氨酸脱羧酶（PvlArgDC）、DNA 修复蛋白（RecO）和孔蛋白（外膜蛋白）作为沙眼衣原体最可行的靶标，这些靶标可能被化合物 NSC_13086、MFCD00276409、MFCD05662003 靶向。缩写沙眼衣原体性传播疾病性传播疾病高吞吐量虚拟筛选 ADMETox 吸收、分布、代谢、排泄和毒性 PMPocketMatchMD 分子动力学模拟 SP 标准精度 XPExtra 精度 MMGBSAMolecular 力学能量与广义 Born 和表面面积连续溶剂化 OMP 外膜蛋白 PvlArgDCPyruvoyl 依赖性精氨酸脱羧酶 RecO 重组蛋白 O。由 Ramaswamy H. Sarma 传达。
