Mapping allostery through computational glycine scanning and correlation analysis of residue-residue contacts.
Mapping allostery through computational glycine scanning and correlation analysis of residue-residue contacts.
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DOI：
10.1021/bi501152d
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发表时间：
2015-02-24
期刊：
影响因子：
2.9
通讯作者：
Shen, Tongye
中科院分区：
文献类型：
--
作者：
Johnson, Quentin R.;Lindsay, Richard J.;Nellas, Ricky B.;Fernandez, Elias J.;Shen, Tongye
了解变构机制对于分子开关和下游细胞反应的物理控制至关重要。然而，在高通量方案中很难解码基本的变构运动。这里提出了一种通用的双管齐下的方法来执行自动数据简化的仿真轨迹。第一步涉及粗粒化和识别最动态的残留物-残留物接触。第二步是对这些接触进行主成分分析，并提取通过这些残余-残余接触表达的大规模集体运动。我们使用核受体的蛋白质复合物证明了该方法。使用原子建模和模拟，我们研究了蛋白质复合物和一组18个甘氨酸点突变的残基，构成的配体效应器的结合口袋。报告了导致变构的重要运动。与传统的诱导配合和锁键结合机制不同，揭示了RXR用于变构控制的新型“受抑配合”结合机制。
Understanding allosteric mechanisms is essential for the physical control of molecular switches and downstream cellular responses. However, it is difficult to decode essential allosteric motions in a high-throughput scheme. A general two-pronged approach to performing automatic data reduction of simulation trajectories is presented here. The first step involves coarse-graining and identifying the most dynamic residue–residue contacts. The second step is performing principal component analysis of these contacts and extracting the large-scale collective motions expressed via these residue–residue contacts. We demonstrated the method using a protein complex of nuclear receptors. Using atomistic modeling and simulation, we examined the protein complex and a set of 18 glycine point mutations of residues that constitute the binding pocket of the ligand effector. The important motions that are responsible for the allostery are reported. In contrast to conventional induced-fit and lock-and-key binding mechanisms, a novel “frustrated-fit” binding mechanism of RXR for allosteric control was revealed.
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影响因子：
2.9
作者：
Imamoto, Y;Kamikubo, H;Kataoka, M
通讯作者：
Kataoka, M
DOI：
10.1073/pnas.96.18.10118
发表时间：
1999-08-31
影响因子：
11.1
作者：
Freire, E
通讯作者：
Freire, E
影响因子：
4.4
作者：
Altis, Alexandros;Nguyen, Phuong H.;Stock, Gerhard
通讯作者：
Stock, Gerhard
DOI：
10.1098/rspb.1926.0064
发表时间：
1926-12-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-CONTAINING PAPERS OF A BIOLOGICAL CHARACTER
影响因子：
--
作者：
Hill, R
通讯作者：
Hill, R
影响因子：
56.9
作者：
COLOMBO, MF;RAU, DC;PARSEGIAN, VA
通讯作者：
PARSEGIAN, VA