High-resolution structural characterization of Noxa, an intrinsically disordered protein, by microsecond molecular dynamics simulations.
High-resolution structural characterization of Noxa, an intrinsically disordered protein, by microsecond molecular dynamics simulations.
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DOI：
10.1039/c5mb00170f
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发表时间：
2015-07
影响因子：
--
通讯作者：
Kelekar A
中科院分区：
文献类型：
--
作者：
Espinoza-Fonseca LM;Kelekar A
高分辨率表征内在无序蛋白质（IDP）的结构和动力学仍然是一项具有挑战性的任务。因此，对IDP的结构和功能特征的详细了解仍然有限，因为很少有全长无序蛋白质被结构表征。我们已经进行了微秒长的分子动力学（MD）模拟的Noxa，最小的成员的大Bcl-2家族的凋亡调节蛋白，在原子水平的细节表征的无序蛋白质的结构特征。从蛋白质的未折叠状态开始的2.5 μs MD模拟显示，在N-和C-末端形成了中心反平行β-折叠结构，两侧是两个无序片段。这种拓扑结构与蛋白质无序预测和现有的实验数据是合理的协议。我们发现，这种折叠起着至关重要的作用，在细胞内的功能和调节Noxa。我们证明了无偏MD模拟结合现代力场揭示了原子级分辨率的无序蛋白质的结构和功能特征。
High-resolution characterization of the structure and dynamics of intrinsically disordered proteins (IDPs) remains a challenging task. Consequently, a detailed understanding of the structural and functional features of IDPs remains limited, as very few full-length disordered proteins have been structurally characterized. We have performed microsecond-long molecular dynamics (MD) simulations of Noxa, the smallest member of the large Bcl-2 family of apoptosis regulating proteins, to characterize in atomic-level detail the structural features of a disordered protein. A 2.5-μs MD simulation starting from an unfolded state of the protein revealed the formation of a central antiparallel β-sheet structure flanked by two disordered segments at the N- and C-terminal ends. This topology is in reasonable agreement with protein disorder predictions and available experimental data. We show that this fold plays an essential role in the intracellular function and regulation of Noxa. We demonstrate that unbiased MD simulations in combination with a modern force field reveal structural and functional features of disordered proteins at atomic-level resolution.
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影响因子：
6.8
作者：
Dunker, A. Keith;Silman, Israel;Sussman, Joel L.
通讯作者：
Sussman, Joel L.
DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.
影响因子：
5.6
作者：
Day, Catherine L.;Smits, Callum;Hinds, Mark G.
通讯作者：
Hinds, Mark G.
影响因子：
5.8
作者：
Dosztányi, Z;Csizmok, V;Simon, I
通讯作者：
Simon, I