Looking at the Disordered Proteins through the Computational Microscope.
Looking at the Disordered Proteins through the Computational Microscope.
复制标题
DOI：
10.1021/acscentsci.7b00626
复制
发表时间：
2018-05-23
影响因子：
18.2
通讯作者：
Mittal J
中科院分区：
文献类型：
--
作者：
Das P;Matysiak S;Mittal J
由于其在蛋白质组中惊人的普遍性和在细胞生理学和病理学中的多功能作用，在过去的十年中，内含子无序蛋白（IDP）引起了广泛的兴趣。大量国内流离失所者已被确定为治疗干预的潜在目标。因此，表征无序蛋白质的结构-功能关系是一项必不可少但艰巨的任务，因为这些蛋白质可以适应瞬时结构，需要一种新的范式将结构紊乱与功能联系起来。分子模拟已经成为对这类有趣的蛋白质的原子级表征和机制研究实验的自然补充。IDP功能中涉及的不同范围的长度和时间尺度需要在多个分辨率级别上执行模拟。在本展望中，我们将重点总结可用的模拟方法，沿着一些有趣的示例应用程序。我们还提供了一个展望，这些模拟方法可以进一步改善，以提供更准确的描述IDP的结构，绑定和组装。精确的计算模型和先进的模拟方法可以帮助识别内在无序蛋白质中的顺序，因为它与它们的（错误）功能有关。
Intrinsically disordered proteins (IDPs) have attracted wide interest over the past decade due to their surprising prevalence in the proteome and versatile roles in cell physiology and pathology. A large selection of IDPs has been identified as potential targets for therapeutic intervention. Characterizing the structure–function relationship of disordered proteins is therefore an essential but daunting task, as these proteins can adapt transient structure, necessitating a new paradigm for connecting structural disorder to function. Molecular simulation has emerged as a natural complement to experiments for atomic-level characterizations and mechanistic investigations of this intriguing class of proteins. The diverse range of length and time scales involved in IDP function requires performing simulations at multiple levels of resolution. In this Outlook, we focus on summarizing available simulation methods, along with a few interesting example applications. We also provide an outlook on how these simulation methods can be further improved in order to provide a more accurate description of IDP structure, binding, and assembly. Accurate computational models and advanced simulation methodologies can help identify order within intrinsically disordered proteins as it relates to their (mis)function.
登录
查看更多内容
影响因子：
4.6
作者：
Chakraborty, Srirupa;Das, Payel
通讯作者：
Das, Payel
影响因子：
2.9
作者：
Cheon, Mookyung;Chang, Iksoo;Hall, Carol K.
通讯作者：
Hall, Carol K.
影响因子：
7.2
作者：
Chen, Bryan;Retzlaff, Marco;Frydman, Judith
通讯作者：
Frydman, Judith
影响因子：
4.8
作者：
Benilova, Iryna;Gallardo, Rodrigo;De Strooper, Bart
通讯作者：
De Strooper, Bart
影响因子：
8.6
作者：
Bonomi, M.;Parrinello, M.
通讯作者：
Parrinello, M.