期刊名称：Computational and Structural Biotechnology Journal
印刷版ISSN：2001-0370
出版年度：2019
卷号：17
页码：570-578
DOI：10.1016/j.csbj.2019.04.011
出版社：Computational and Structural Biotechnology Journal
摘要：Proteins and protein complexes with high conformational flexibility participate in a wide range of biological processes. These processes include genome maintenance, gene expression, signal transduction, cell cycle regulation, and many others. Gaining a structural understanding of conformationally flexible proteins and protein complexes is arguably the greatest problem facing structural biologists today. Over the last decade, some progress has been made toward understanding the conformational flexibility of such systems using hybrid approaches. One particularly fruitful strategy has been the combination of small-angle X-ray scattering (SAXS) and molecular simulations. In this article, we provide a brief overview of SAXS and molecular simulations and then discuss two general approaches for combining SAXS data and molecular simulations: minimal ensemble approaches and full ensemble approaches. In minimal ensemble approaches, one selects a minimal ensemble of structures from the simulations that best fit the SAXS data. In full ensemble approaches, one validates a full ensemble of structures from the simulations using SAXS data. We argue that full ensemble models are more realistic than minimal ensemble searches models and that full ensemble approaches should be used wherever possible.
关键词：DNA replication ; DNA polymerase ; Minimal ensemble search ; Protein structure ; SANS ; SAXS ; BD Brownian dynamics ; CG coarse-grained ; Cryo-EM cryo-electron microscopy ; Dmax maximal distance ; LD Langevin dynamics ; MD molecular dynamics ; NMR nuclear magnetic resonance ; PCNA proliferating cell nuclear antigen ; Pol η DNA polymerase eta ; Rg radius of gyration ; RPA replication protein A ; SANS small-angle neutron scattering ; SAXS small-angle X-ray scattering ; SEC size exclusion chromatography ; SUMO small ubiquitin-like modifie
