RNA tertiary structure analysis by 2?-Hydroxyl molecular interference

Philip J. Homan; Arpit Tandon; Greggory M. Rice; Feng Ding; Nikolay V. Dokholyan; Kevin M. Weeks

doi:10.1021/bi501218g

RNA tertiary structure analysis by 2?-Hydroxyl molecular interference

Philip J. Homan, Arpit Tandon, Greggory M. Rice, Feng Ding, Nikolay V. Dokholyan, Kevin M. Weeks

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

We introduce a melded chemical and computational approach for probing and modeling higher-order intramolecular tertiary interactions in RNA. 2?- molecular interference (HMX) identifies nucleotides in highly packed regions of an RNA by exploiting the ability of bulky adducts at the 2?-hydroxyl position to disrupt overall RNA structure. HMX was found to be exceptionally selective for quantitative detection of higher-order and tertiary interactions. When incorporated as experimental constraints in discrete molecular dynamics simulations, HMX information yielded accurate three-dimensional models, emphasizing the power of molecular interference to guide RNA tertiary structure analysis and fold refinement. In the case of a large, multidomain RNA, the Tetrahymena group I intron, HMX identified multiple distinct sets of tertiary structure interaction groups in a single, concise experiment.

Original language	English (US)
Pages (from-to)	6825-6833
Number of pages	9
Journal	Biochemistry
Volume	53
Issue number	43
DOIs	https://doi.org/10.1021/bi501218g
State	Published - Nov 4 2014

All Science Journal Classification (ASJC) codes

Biochemistry

Access to Document

10.1021/bi501218g

Cite this

@article{4b72e7ed16b946a9b11d3ff01c605fde,

title = "RNA tertiary structure analysis by 2?-Hydroxyl molecular interference",

abstract = "We introduce a melded chemical and computational approach for probing and modeling higher-order intramolecular tertiary interactions in RNA. 2?- molecular interference (HMX) identifies nucleotides in highly packed regions of an RNA by exploiting the ability of bulky adducts at the 2?-hydroxyl position to disrupt overall RNA structure. HMX was found to be exceptionally selective for quantitative detection of higher-order and tertiary interactions. When incorporated as experimental constraints in discrete molecular dynamics simulations, HMX information yielded accurate three-dimensional models, emphasizing the power of molecular interference to guide RNA tertiary structure analysis and fold refinement. In the case of a large, multidomain RNA, the Tetrahymena group I intron, HMX identified multiple distinct sets of tertiary structure interaction groups in a single, concise experiment.",

author = "Homan, {Philip J.} and Arpit Tandon and Rice, {Greggory M.} and Feng Ding and Dokholyan, {Nikolay V.} and Weeks, {Kevin M.}",

note = "Publisher Copyright: {\textcopyright} 2014 American Chemical Society.",

year = "2014",

month = nov,

day = "4",

doi = "10.1021/bi501218g",

language = "English (US)",

volume = "53",

pages = "6825--6833",

journal = "Biochemistry",

issn = "0006-2960",

publisher = "American Chemical Society",

number = "43",

}

TY - JOUR

T1 - RNA tertiary structure analysis by 2?-Hydroxyl molecular interference

AU - Homan, Philip J.

AU - Tandon, Arpit

AU - Rice, Greggory M.

AU - Ding, Feng

AU - Dokholyan, Nikolay V.

AU - Weeks, Kevin M.

PY - 2014/11/4

Y1 - 2014/11/4

N2 - We introduce a melded chemical and computational approach for probing and modeling higher-order intramolecular tertiary interactions in RNA. 2?- molecular interference (HMX) identifies nucleotides in highly packed regions of an RNA by exploiting the ability of bulky adducts at the 2?-hydroxyl position to disrupt overall RNA structure. HMX was found to be exceptionally selective for quantitative detection of higher-order and tertiary interactions. When incorporated as experimental constraints in discrete molecular dynamics simulations, HMX information yielded accurate three-dimensional models, emphasizing the power of molecular interference to guide RNA tertiary structure analysis and fold refinement. In the case of a large, multidomain RNA, the Tetrahymena group I intron, HMX identified multiple distinct sets of tertiary structure interaction groups in a single, concise experiment.

AB - We introduce a melded chemical and computational approach for probing and modeling higher-order intramolecular tertiary interactions in RNA. 2?- molecular interference (HMX) identifies nucleotides in highly packed regions of an RNA by exploiting the ability of bulky adducts at the 2?-hydroxyl position to disrupt overall RNA structure. HMX was found to be exceptionally selective for quantitative detection of higher-order and tertiary interactions. When incorporated as experimental constraints in discrete molecular dynamics simulations, HMX information yielded accurate three-dimensional models, emphasizing the power of molecular interference to guide RNA tertiary structure analysis and fold refinement. In the case of a large, multidomain RNA, the Tetrahymena group I intron, HMX identified multiple distinct sets of tertiary structure interaction groups in a single, concise experiment.

UR - http://www.scopus.com/inward/record.url?scp=84908568378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908568378&partnerID=8YFLogxK

U2 - 10.1021/bi501218g

DO - 10.1021/bi501218g

M3 - Article

C2 - 25341083

AN - SCOPUS:84908568378

SN - 0006-2960

VL - 53

SP - 6825

EP - 6833

JO - Biochemistry

JF - Biochemistry

IS - 43

ER -

RNA tertiary structure analysis by 2?-Hydroxyl molecular interference

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this