Rossetti Giulia, Dibenedetto Domenica, Calandrini Vania, Giorgetti Alejandro, Carloni Paolo
Computational Biophysics, German Research School for Simulation Sciences, and Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, 52425 Jülich, Germany; Jülich Supercomputing Centre, Forschungszentrum Jülich, 52425 Jülich, Germany.
Computational Biophysics, German Research School for Simulation Sciences, and Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, 52425 Jülich, Germany.
Arch Biochem Biophys. 2015 Sep 15;582:91-100. doi: 10.1016/j.abb.2015.03.011. Epub 2015 Mar 19.
G protein coupled receptors (GPCRs) and intrinsic disordered proteins (IDPs) are key players for neuronal function and dysfunction. Unfortunately, their structural characterization is lacking in most cases. From one hand, no experimental structure has been determined for the two largest GPCRs subfamilies, both key proteins in neuronal pathways. These are the odorant (450 members out of 900 human GPCRs) and the bitter taste receptors (25 members) subfamilies. On the other hand, also IDPs structural characterization is highly non-trivial. They exist as dynamic, highly flexible structural ensembles that undergo conformational conversions on a wide range of timescales, spanning from picoseconds to milliseconds. Computational methods may be of great help to characterize these neuronal proteins. Here we review recent progress from our lab and other groups to develop and apply in silico methods for structural predictions of these highly relevant, fascinating and challenging systems.
G蛋白偶联受体（GPCRs）和内在无序蛋白（IDPs）是神经元功能及功能障碍的关键因素。遗憾的是，在大多数情况下，它们的结构特征尚不明确。一方面，神经元通路中的两个最大的GPCRs亚家族，尚未确定实验结构，而这两个亚家族都是关键蛋白。它们分别是嗅觉受体亚家族（在900个人类GPCRs中有450个成员）和苦味受体亚家族（25个成员）。另一方面，内在无序蛋白的结构表征也极具挑战性。它们以动态、高度灵活的结构集合形式存在，会在从皮秒到毫秒的广泛时间尺度上发生构象转换。计算方法可能对表征这些神经元蛋白有很大帮助。在此，我们综述了我们实验室和其他团队最近在开发和应用计算机方法对这些高度相关、引人入胜且具有挑战性的系统进行结构预测方面取得的进展。
