Insights into the energy landscapes of chromosome organization proteins from coevolutionary sequence variation and structural modeling
Insights into the energy landscapes of chromosome organization proteins from coevolutionary sequence variation and structural modeling
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从共同进化序列变异和结构建模洞察染色体组织蛋白的能量景观
DOI：
10.1073/pnas.1921727117
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Levy, Ronald M.
中科院分区：
文献类型：
--
作者：
Levy, Ronald M.
直接偶联分析（DCA）是一种量化生物序列上两个位置之间直接相互作用强度的方法。它已被用于推断有关分子内和分子间蛋白质-蛋白质接触的结构信息，以及与蛋白质适应性相关的信息，并使用最大熵推断来产生受统计物理学启发的观察到的序列变化的“Potts”Hamilton模型（3-5）。使用DCA和晶体学数据（6，7），Onuchic和同事（8）以前能够构建整个凝聚素复合物的原子尺度模型，这为染色体组织蛋白质的能量景观分析提供了起点参考文献2报告。使用粗粒度AWSEM（9）对细菌和真核细胞内聚和凝聚进行分子动力学（MD）模拟。应该注意的是，目前可用的结构信息不足以明确地确定染色体组织蛋白的编织拓扑结构的分布，或卷曲螺旋区域的异质性的其他特征，这些特征可能对功能很重要。用AWSEM的MD模拟在两个关键的方式来补充实验确定的结构和共同进化的信息。首先，有可能表明，在初始模型中，最小受抑接触和高度受抑接触的比例与通常在蛋白质晶体结构中观察到的比例一致。其次，粗粒度MD模拟a生物物理和计算生物学中心，天普大学，费城，宾夕法尼亚州19122;和b天普大学化学系，费城，宾夕法尼亚州19122
Direct coupling analysis (DCA) is a method to quantify the strength of the direct interaction between two positions on a biological sequence. It has been used to infer structural information about intra-and intermolecular protein–protein contacts, as well as information related to protein fitness, and uses maximum entropy inference to produce a “Potts” Hamiltonian model of the observed sequence variation inspired by statistical physics (3–5). Using DCA together with crystallographic data (6, 7), Onuchic and coworkers (8) were previously able to construct an atomic-scale model of the whole condensin complex, which provides a starting point for the energy landscape analysis of chromosome organization proteins ref. 2 reports. Molecular dynamics (MD) simulations of the bacterial and eukaryotic cohesion and condensin were performed using the coarse-grained AWSEM (9). It should be noted that the currently available structural information is insufficient to unambiguously determine the distribution of braiding topologies of chromosomal organization proteins, or other features of the heterogeneity of the coiled-coil regions which are likely to be important for function. The MD simulations with AWSEM were used in two key ways to supplement the experimentally determined structural and coevolutionary information. First, it was possible to show that the proportion of minimally frustrated contacts and highly frustrated contacts in the starting models were consistent with those generally observed in protein crystal structures. Second, the coarse-grained MD simulations aCenter for Biophysics and Computational Biology, Temple University, Philadelphia, PA 19122; and bDepartment of Chemistry, Temple University, Philadelphia, PA 19122
DOI：
10.1073/pnas.1917750117
发表时间：
2020-01-21
影响因子：
11.1
作者：
Krepel, Dana;Davtyan, Aram;Onuchic, Jose N.
通讯作者：
Onuchic, Jose N.