Uncovering mechanisms of protein function is challenging when structural characterization of the functionally relevant states is elusive, for instance for large and flexible proteins which resist crystallization. This is the case for structural maintenance of chromosomes (SMC) proteins and kleisin subunits which are crucial for the segregation of chromosomes during cell division but whose mechanism to organize chromosomes for replication is not known. The two most prominent multisubunit SMC complexes are cohesin and condensin, which form large complexes (more than 650 kDa for condensin) containing long antiparallel coiled coils, making them difficult to study by conventional crystallography or cryoelectron microscopy. Integrative structural biology techniques have arisen in response to these challenges which attempt to solve the puzzle by combining incomplete information from diverse experimental data with computational and theoretical results (1). In PNAS, Krepel et al. (2) use an integrative approach to understanding the mechanism of SMC action which incorporates evolutionary sequence analysis with molecular simulations based on an energy landscape optimized effective potential (AWSEM, associative memory, water-mediated, structure and energy model) along with crystallographic structural information and cross-linking experimental data to map features of the conformational and energy landscapes of SMC proteins. A complete atom-level structural model of …

中文翻译：

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从协同进化序列变异和结构建模中洞悉染色体组织蛋白的能量分布。

当对功能相关状态的结构表征难以捉摸时，例如对于抵抗结晶的大而柔软的蛋白质，蛋白质功能的揭示机理就具有挑战性。染色体（SMC）蛋白质和kleisin亚基的结构维持就是这种情况，它们对于细胞分裂过程中的染色体分离至关重要，但其组织染色体复制的机制尚不清楚。两种最突出的多亚基SMC复合物是粘着素和凝聚素，它们形成了大的复合物（凝聚素超过650 kDa），其中包含长的反平行螺旋线圈，这使得它们很难通过常规的晶体学或低温电子显微镜进行研究。1）。在PNAS中，Krepel等人。（2）使用一种综合方法来理解SMC作用的机理，该方法将进化序列分析与分子模拟相结合，该分子模拟基于能效最优化的有效势（AWSEM，缔合记忆，水介导，结构和能量模型）以及晶体学结构信息以及交联实验数据以绘制SMC蛋白构象和能量构图的特征。…的完整原子级结构模型