Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel; email:
School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel; email:
Annu Rev Biochem. 2019 Jun 20;88:113-135. doi: 10.1146/annurev-biochem-013118-111429. Epub 2019 Mar 4.
Integrative structure modeling computationally combines data from multiple sources of information with the aim of obtaining structural insights that are not revealed by any single approach alone. In the first part of this review, we survey the commonly used sources of structural information and the computational aspects of model building. Throughout the past decade, integrative modeling was applied to various biological systems, with a focus on large protein complexes. Recent progress in the field of cryo-electron microscopy (cryo-EM) has resolved many of these complexes to near-atomic resolution. In the second part of this review, we compare a range of published integrative models with their higher-resolution counterparts with the aim of critically assessing their accuracy. This comparison gives a favorable view of integrative modeling and demonstrates its ability to yield accurate and informative results. We discuss possible roles of integrative modeling in the new era of cryo-EM and highlight future challenges and directions.
整合结构建模通过计算将来自多个信息源的数据结合起来，旨在获得仅凭任何单一方法都无法揭示的结构见解。在本综述的第一部分，我们调查了常用的结构信息来源和建模的计算方面。在过去的十年中，整合建模已应用于各种生物系统，重点是大型蛋白质复合物。冷冻电子显微镜（cryo-EM）领域的最新进展已将其中许多复合物解析至近原子分辨率。在本综述的第二部分，我们将一系列已发表的整合模型与其高分辨率对应物进行比较，目的是批判性地评估它们的准确性。这种比较对整合建模持有利观点，并证明了它能够产生准确和有信息的结果。我们讨论了整合建模在 cryo-EM 的新时代可能发挥的作用，并强调了未来的挑战和方向。
