RNA Structure Determination by Structural Probing and Mass Spectrometry: MS3D

Chapter
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC, volume 27)

Abstract

Recent advances of detection strategies based on mass spectrometry (MS) have reawakened the interest in chemical methods for RNA structural elucidation by enabling experimental protocols that minimize their typical pitfalls. At the same time, the development of ever more sophisticated modeling techniques has helped close the resolution gap by providing atomic-level details that were previously beyond reach. Here, we describe the integration of MS-assisted structural probing with appropriate computational techniques, which has been termed MS3D, and illustrate its application to the elucidation of RNA substrates of biological significance. We address typical concerns faced by probing applications and possible solutions supported by the MS platform. We describe strategies for translating sparse spatial constraints afforded by footprinting and cross-linking reagents into testable all-atom structures. We also discuss future advances that would take further advantage of the synergy between experimental and computational approaches to increase the accuracy of chemical methods and to expand their scope to progressively larger and more complex targets.

Keywords

Mouse Mammary Tumor Virus Bifunctional Reagent Monofunctional Adduct Crick Pairing Substrate Dynamic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by National Institutes of Health Grant GM643208 and National Science Foundation Grant CHE-0439067.

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.University of Maryland Baltimore CountyCatonsvilleUSA
  2. 2.The RNA InstituteUniversity at AlbanyAlbanyUSA

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