title: An Integrated Spin-Labeling/Computational-Modeling Approach for Mapping Global Structures of Nucleic Acids.
abstract: The technique of site-directed spin labeling (SDSL) provides unique information on biomolecules by monitoring the behavior of a stable radical tag (i.e., spin label) using electron paramagnetic resonance (EPR) spectroscopy. In this chapter, we describe an approach in which SDSL is integrated with computational modeling to map conformations of nucleic acids. This approach builds upon a SDSL tool kit previously developed and validated, which includes three components: (i) a nucleotide-independent nitroxide probe, designated as R5, which can be efficiently attached at defined sites within arbitrary nucleic acid sequences; (ii) inter-R5 distances in the nanometer range, measured via pulsed EPR; and (iii) an efficient program, called NASNOX, that computes inter-R5 distances on given nucleic acid structures. Following a general framework of data mining, our approach uses multiple sets of measured inter-R5 distances to retrieve "correct" all-atom models from a large ensemble of models. The pool of models can be generated independently without relying on the inter-R5 distances, thus allowing a large degree of flexibility in integrating the SDSL-measured distances with a modeling approach best suited for the specific system under investigation. As such, the integrative experimental/computational approach described here represents a hybrid method for determining all-atom models based on experimentally-derived distance measurements.
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, USA.
authors.forename: Narin S
authors.initials: NS
authors.lastname: Tangprasertchai
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Tham
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, USA; Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California, USA.
authors.forename: Remo
authors.initials: R
authors.lastname: Rohs
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Haworth
authors.affiliation: Department of Chemistry, University of Southern California, Los Angeles, California, USA; Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, California, USA. Electronic address: pzq@usc.edu.
authors.forename: Peter Z
authors.initials: PZ
authors.lastname: Qin
mesh_terms: D003198:Computer Simulation; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D009589:Nitrogen Oxides / Q000032:analysis; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry*; D013113:Spin Labels
chemical_list: D009589:Nitrogen Oxides; D009696:Nucleic Acids; D013113:Spin Labels; C039900:nitroxyl
keywords: DEER; DNA; EPR; Hybrid models; Integrative modeling; Protein–DNA binding; RNA; Site-directed spin labeling; Solution-state structure