Detection and characterization of nonspecific, sparsely populated binding modes in the early stages of complexation.
Detection and characterization of nonspecific, sparsely populated binding modes in the early stages of complexation.
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DOI：
10.1002/jcc.23883
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发表时间：
2015-05-15
影响因子：
3
通讯作者：
Hassan, Sergio A.
中科院分区：
文献类型：
--
作者：
Cardone, Antonio;Bornstein, Aaron;Pant, Harish C.;Brady, Mary;Sriram, Ram;Hassan, Sergio A.
关键词：
提出了一种研究由特异性和非特异性相互作用控制的系统中蛋白质-配体结合的方法。强关联导致蛋白质构型空间的窄分布；弱关联和超弱关联会导致更广泛的分布，这是具有多个接口的非特异性、稀疏的结合模式的表现。该方法基于这样的概念：一组离散的优先首次相遇模式是亚稳态，在平衡状态下稳定（预弛豫）配合物从亚稳态演化而来。该方法可用于探索具有统计显着性的络合替代途径，并可集成到研究蛋白质相互作用网络的通用算法中。该方法适用于肽-蛋白质复合物。该肽采用多种低数量构象异构体，并以多种模式结合，具有广泛的亲和力。因此，该系统非常适合分析结合的一般特征，包括构象选择、结合模式的多样性和非特异性相互作用，并说明如何应用该方法来系统地研究这些问题。平衡分布可用于生成用于模拟多蛋白质系统的偏置函数，从中可以计算大量热力学量。
A method is proposed to study protein-ligand binding in a system governed by specific and non-specific interactions. Strong associations lead to narrow distributions in the proteins configuration space; weak and ultra-weak associations lead instead to broader distributions, a manifestation of non-specific, sparsely-populated binding modes with multiple interfaces. The method is based on the notion that a discrete set of preferential first-encounter modes are metastable states from which stable (pre-relaxation) complexes at equilibrium evolve. The method can be used to explore alternative pathways of complexation with statistical significance and can be integrated into a general algorithm to study protein interaction networks. The method is applied to a peptide-protein complex. The peptide adopts several low-population conformers and binds in a variety of modes with a broad range of affinities. The system is thus well suited to analyze general features of binding, including conformational selection, multiplicity of binding modes, and nonspecific interactions, and to illustrate how the method can be applied to study these problems systematically. The equilibrium distributions can be used to generate biasing functions for simulations of multiprotein systems from which bulk thermodynamic quantities can be calculated.
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影响因子：
64.8
作者：
Endy, D;Brent, R
通讯作者：
Brent, R
DOI：
10.1016/b978-0-12-374920-8.00916-4
发表时间：
2011-01-01
期刊：
COMPREHENSIVE BIOPHYSICS, VOL 9: SIMULATION AND MODELLING
影响因子：
--
作者：
Hassan, S. A.;Mehler, E. L.
通讯作者：
Mehler, E. L.
影响因子：
3.3
作者：
Hassan, SA
通讯作者：
Hassan, SA
影响因子：
13.8
作者：
Csermely, Peter;Palotai, Robin;Nussinov, Ruth
通讯作者：
Nussinov, Ruth
影响因子：
3
作者：
Baba, Takeshi;Harada, Ryuhei;Shigeta, Yasuteru
通讯作者：
Shigeta, Yasuteru