Zhang Zhiyong, Voth Gregory A
Department of Chemistry, James Franck and Computation Institutes, University of Chicago, 5735 S. Ellis Avenue, Chicago, Illinois 60637.
J Chem Theory Comput. 2010 Sep 14;6(9):2990-3002. doi: 10.1021/ct100374a. Epub 2010 Aug 23.
High-resolution atomistic structures of many large biomolecular complexes have not yet been solved by experiments, such as X-ray crystallography or NMR. Often however low-resolution information is obtained by alternative techniques, such as cryo-electron microscopy or small-angle X-ray scattering. Coarse-grained (CG) models are an appropriate choice to computationally study these complexes given the limited resolution experimental data. One of the important questions therefore is how to define CG representations from these low-resolution density maps. This work provides a space-based essential dynamics coarse-graining (ED-CG) method to define a CG representation from a density map without detailed knowledge of its underlying atomistic structure and primary sequence information. This method is demonstrated on G-actin (both the atomic structure and its density map). It is then applied to the density maps of the Escherichia coli 70S ribosome and the microtubule. The results indicate that the method can define highly CG models that still preserve functionally important dynamics of large biomolecular complexes.
许多大型生物分子复合物的高分辨率原子结构尚未通过诸如X射线晶体学或核磁共振等实验方法得到解析。然而，通常可以通过诸如冷冻电子显微镜或小角X射线散射等替代技术获得低分辨率信息。鉴于实验数据分辨率有限，粗粒度（CG）模型是对这些复合物进行计算研究的合适选择。因此，一个重要的问题是如何从这些低分辨率密度图定义CG表示。这项工作提供了一种基于空间的本质动力学粗粒化（ED-CG）方法，用于从密度图定义CG表示，而无需详细了解其潜在的原子结构和一级序列信息。该方法在G-肌动蛋白（包括其原子结构及其密度图）上得到了验证。然后将其应用于大肠杆菌70S核糖体和微管的密度图。结果表明，该方法可以定义高度粗粒化的模型，这些模型仍然保留了大型生物分子复合物的功能重要动力学。
