title: Integrative Modeling of Macromolecular Assemblies from Low to Near-Atomic Resolution.
abstract: While conventional high-resolution techniques in structural biology are challenged by the size and flexibility of many biological assemblies, recent advances in low-resolution techniques such as cryo-electron microscopy (cryo-EM) and small angle X-ray scattering (SAXS) have opened up new avenues to define the structures of such assemblies. By systematically combining various sources of structural, biochemical and biophysical information, integrative modeling approaches aim to provide a unified structural description of such assemblies, starting from high-resolution structures of the individual components and integrating all available information from low-resolution experimental methods. In this review, we describe integrative modeling approaches, which use complementary data from either cryo-EM or SAXS. Specifically, we focus on the popular molecular dynamics flexible fitting (MDFF) method, which has been widely used for flexible fitting into cryo-EM maps. Second, we describe hybrid molecular dynamics, Rosetta Monte-Carlo and minimum ensemble search (MES) methods that can be used to incorporate SAXS into pseudoatomic structural models. We present concise descriptions of the two methods and their most popular alternatives, along with select illustrative applications to protein/nucleic acid assemblies involved in DNA replication and repair.
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Chunli
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wohlhueter
authors.affiliation: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA.
authors.forename: Ivaylo
authors.initials: I
authors.lastname: Ivanov
keywords: DNA replication and repair; Electron microscopy (EM); Hybrid modeling; Integrative modeling; Molecular dynamics flexible fitting (MDFF); Small angle X-ray scattering (SAXS)