Synergy between NMR measurements and MD simulations of
protein/RNA complexes: application to the RRMs, the most common
RNA recognition motifs

J 2016

Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs

KREPL, Miroslav; Antoine CLERY; Markus BLATTER; Frederic H. T. ALLAIN; Jiří ŠPONER et. al.

Základní údaje

Originální název

Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs

Autoři

KREPL, Miroslav (203 Česká republika); Antoine CLERY (756 Švýcarsko); Markus BLATTER (756 Švýcarsko); Frederic H. T. ALLAIN (756 Švýcarsko) a Jiří ŠPONER (203 Česká republika, garant, domácí)

Vydání

Nucleic Acids Research, Oxford, Oxford University Press, 2016, 0305-1048

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 10.162

Kód RIV

RIV/00216224:14740/16:00088219

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1093/nar/gkw438

UT WoS

000382999300041

EID Scopus

2-s2.0-84982782570

Klíčová slova anglicky

MOLECULAR-DYNAMICS SIMULATIONS; PARTICLE MESH EWALD; PRE-RIBOSOMAL-RNA; FORCE-FIELD; CAENORHABDITIS-ELEGANS; BACKBONE PARAMETERS; SPLICING FACTORS; STRUCTURAL BASIS; NUCLEIC-ACIDS; SR PROTEINS

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 6. 1. 2017 12:05, Mgr. Eva Špillingová

Anotace

V originále

RNA recognition motif (RRM) proteins represent an abundant class of proteins playing key roles in RNA biology. We present a joint atomistic molecular dynamics (MD) and experimental study of two RRM-containing proteins bound with their single-stranded target RNAs, namely the Fox-1 and SRSF1 complexes. The simulations are used in conjunction with NMR spectroscopy to interpret and expand the available structural data. We accumulate more than 50 mu s of simulations and show that the MD method is robust enough to reliably describe the structural dynamics of the RRM-RNA complexes. The simulations predict unanticipated specific participation of Arg142 at the protein-RNA interface of the SRFS1 complex, which is subsequently confirmed by NMR and ITC measurements. Several segments of the protein-RNA interface may involve competition between dynamical local substates rather than firmly formed interactions, which is indirectly consistent with the primary NMR data. We demonstrate that the simulations can be used to interpret the NMR atomistic models and can provide qualified predictions. Finally, we propose a protocol for 'MD-adapted structure ensemble' as a way to integrate the simulation predictions and expand upon the deposited NMR structures. Unbiased mu s-scale atomistic MD could become a technique routinely complementing the NMR measurements of protein-RNA complexes.

Návaznosti

GBP305/12/G034, projekt VaV

Název: Centrum biologie RNA

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

KREPL, Miroslav; Antoine CLERY; Markus BLATTER; Frederic H. T. ALLAIN a Jiří ŠPONER. Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs. Nucleic Acids Research. Oxford: Oxford University Press, 2016, roč. 44, č. 13, s. 6452-6470. ISSN 0305-1048. Dostupné z: https://doi.org/10.1093/nar/gkw438.

@article{1356112,
   author = {Krepl, Miroslav and Clery, Antoine and Blatter, Markus and Allain, Frederic H. T. and Šponer, Jiří},
   article_location = {Oxford},
   article_number = {13},
   doi = {https://doi.org/10.1093/nar/gkw438},
   keywords = {MOLECULAR-DYNAMICS SIMULATIONS; PARTICLE MESH EWALD; PRE-RIBOSOMAL-RNA; FORCE-FIELD; CAENORHABDITIS-ELEGANS; BACKBONE PARAMETERS; SPLICING FACTORS; STRUCTURAL BASIS; NUCLEIC-ACIDS; SR PROTEINS},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs},
   url = {http://nar.oxfordjournals.org/content/44/13/6452.full.pdf+html},
   volume = {44},
   year = {2016}
}

TY  - JOUR
ID  - 1356112
AU  - Krepl, Miroslav - Clery, Antoine - Blatter, Markus - Allain, Frederic H. T. - Šponer, Jiří
PY  - 2016
TI  - Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs
JF  - Nucleic Acids Research
VL  - 44
IS  - 13
SP  - 6452-6470
EP  - 6452-6470
PB  - Oxford University Press
SN  - 03051048
KW  - MOLECULAR-DYNAMICS SIMULATIONS
KW  - PARTICLE MESH EWALD
KW  - PRE-RIBOSOMAL-RNA
KW  - FORCE-FIELD
KW  - CAENORHABDITIS-ELEGANS
KW  - BACKBONE PARAMETERS
KW  - SPLICING FACTORS
KW  - STRUCTURAL BASIS
KW  - NUCLEIC-ACIDS
KW  - SR PROTEINS
UR  - http://nar.oxfordjournals.org/content/44/13/6452.full.pdf+html
L2  - http://nar.oxfordjournals.org/content/44/13/6452.full.pdf+html
N2  - RNA recognition motif (RRM) proteins represent an abundant class of proteins playing key roles in RNA biology. We present a joint atomistic molecular dynamics (MD) and experimental study of two RRM-containing proteins bound with their single-stranded target RNAs, namely the Fox-1 and SRSF1 complexes. The simulations are used in conjunction with NMR spectroscopy to interpret and expand the available structural data. We accumulate more than 50 mu s of simulations and show that the MD method is robust enough to reliably describe the structural dynamics of the RRM-RNA complexes. The simulations predict unanticipated specific participation of Arg142 at the protein-RNA interface of the SRFS1 complex, which is subsequently confirmed by NMR and ITC measurements. Several segments of the protein-RNA interface may involve competition between dynamical local substates rather than firmly formed interactions, which is indirectly consistent with the primary NMR data. We demonstrate that the simulations can be used to interpret the NMR atomistic models and can provide qualified predictions. Finally, we propose a protocol for 'MD-adapted structure ensemble' as a way to integrate the simulation predictions and expand upon the deposited NMR structures. Unbiased mu s-scale atomistic MD could become a technique routinely complementing the NMR measurements of protein-RNA complexes.
ER  -

KREPL, Miroslav; Antoine CLERY; Markus BLATTER; Frederic H. T. ALLAIN a Jiří ŠPONER. Synergy between NMR measurements and MD simulations of protein/RNA complexes: application to the RRMs, the most common RNA recognition motifs. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2016, roč.~44, č.~13, s.~6452-6470. ISSN~0305-1048. Dostupné z: https://doi.org/10.1093/nar/gkw438.

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