根据世界卫生组织（世卫组织）公布的统计数据，tuberculosis (TB) is globally one of the leading causes of death from a curable infectious disease.While antibiotics represent a major breakthrough for modern medicine,多药耐药（MDR）菌株的传播，如结核分枝杆菌，已经成为医疗保健的主要威胁。
令人鼓舞的是，renewed efforts in antibiotic research have resulted in the identification of new leads,其中一些目前正在进行临床试验。Even in light of these promising efforts,博士。达勒姆大学的Ehmke Pohland collaborators from the Cambridge Crystallographic Data Centre and Institut Pasteur de Lille are emphasizing the need to optimize existing TB treatments as well as develop an efficient means of identifying novel therapeutics.
Structure-based drug discovery is an integral part of most industrial drug discovery programs and as a result,there is an ever-growing number of protein X-ray crystal structures available in databases such as the Protein Data Bank (PDB).Pohl and collaborators outline a robust and versatile strategy for an生物信息学基于锌数据库中的化合物（商业上可买到的化合物的免费资源）和PDB中晶体结构的筛选方案。
它们电流OBC学习focuses on the transcriptional regulator EthR which is involved inM.结核病resistance.已经证明，通过下调参与乙酰亚胺前药激活的乙酰亚胺酶，乙酰亚胺可以限制乙酰亚胺类药物的疗效。EthR has therefore been validated as a suitable target as its inhibition boosts ethionamide action.
Using tailored chemical and physicochemical descriptors (for example: compound volume) and a detailed knowledge of the EthR binding pocket,使用Knime管道软件评估了大约600万种化合物的相容性。409 201 diverse compounds were identified for docking studies and surprisingly,only 6 compounds failed to produce feasible binding interactions.经过仔细的对接后过滤器，284 chemically diverse compounds were obtained and a visual analysis of all binding poses and ligand geometries in combination with computational analysis narrowed the screen down to 85 substrates.这些生物信息学然后，利用热蛋白稳定性研究对其与ethr结合的能力进行评估，结果发现20种新的潜在的铅优化候选物具有合理的EC。50价值观。
考虑到PDB中越来越多的高分辨率晶体结构，生物信息学筛选方法可以针对任何特征明确的蛋白质结构进行调整，并用作识别新活性分子的有效工具。
要了解更多信息，请参阅：
New active leads for tuberculosis booster drugs by structure-based drug discovery
娜塔利J。塔特姆
DOI:10.1039/C7OB00910K
维多利亚·科勒斯目前正在完成她的博士学位。在有机化学方面与教授新利手机客户端Andrei Yudin at the University of Toronto.Her research is centred on the synthesis of kinetically amphoteric building blocks which offer a versatile platform for the development of chemoselective transformations with particular emphasis on creating novel biologically active molecules.
