Spontaneous binding of single-stranded RNAs to RRM proteins
visualized by unbiased atomistic simulations with a rescaled
RNA force field

J 2022

Spontaneous binding of single-stranded RNAs to RRM proteins visualized by unbiased atomistic simulations with a rescaled RNA force field

KREPL, Miroslav, Pavlína POKORNÁ, Vojtěch MLÝNSKÝ, Petr STADLBAUER, Jiří ŠPONER et. al.

Basic information

Original name

Spontaneous binding of single-stranded RNAs to RRM proteins visualized by unbiased atomistic simulations with a rescaled RNA force field

Authors

KREPL, Miroslav (203 Czech Republic, guarantor), Pavlína POKORNÁ (203 Czech Republic, belonging to the institution), Vojtěch MLÝNSKÝ, Petr STADLBAUER (203 Czech Republic) and Jiří ŠPONER (203 Czech Republic)

Edition

Nucleic Acids Research, Oxford University Press, 2022, 0305-1048

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 14.900

RIV identification code

RIV/00216224:14310/22:00128192

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1093/nar/gkac1106

UT WoS

000910551800001

Keywords in English

protein/RNA complexes; RRM proteins; atomistic simulations

Abstract

V originále

Recognition of single-stranded RNA (ssRNA) by RNA recognition motif (RRM) domains is an important class of protein–RNA interactions. Many such complexes were characterized using nuclear magnetic resonance (NMR) and/or X-ray crystallography techniques, revealing ensemble-averaged pictures of the bound states. However, it is becoming widely accepted that better understanding of protein–RNA interactions would be obtained from ensemble descriptions. Indeed, earlier molecular dynamics simulations of bound states indicated visible dynamics at the RNA–RRM interfaces. Here, we report the first atomistic simulation study of spontaneous binding of short RNA sequences to RRM domains of HuR and SRSF1 proteins. Using a millisecond-scale aggregate ensemble of unbiased simulations, we were able to observe a few dozen binding events. HuR RRM3 utilizes a pre-binding state to navigate the RNA sequence to its partially disordered bound state and then to dynamically scan its different binding registers. SRSF1 RRM2 binding is more straightforward but still multiple-pathway. The present study necessitated development of a goal-specific force field modification, scaling down the intramolecular van der Waals interactions of the RNA which also improves description of the RNA–RRM bound state. Our study opens up a new avenue for large-scale atomistic investigations of binding landscapes of protein–RNA complexes, and future perspectives of such research are discussed.

Links

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

KREPL, Miroslav, Pavlína POKORNÁ, Vojtěch MLÝNSKÝ, Petr STADLBAUER and Jiří ŠPONER. Spontaneous binding of single-stranded RNAs to RRM proteins visualized by unbiased atomistic simulations with a rescaled RNA force field. Nucleic Acids Research. Oxford University Press, 2022, vol. 50, No 21, p. 12480-12496. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkac1106.

@article{2248162,
   author = {Krepl, Miroslav and Pokorná, Pavlína and Mlýnský, Vojtěch and Stadlbauer, Petr and Šponer, Jiří},
   article_number = {21},
   doi = {http://dx.doi.org/10.1093/nar/gkac1106},
   keywords = {protein/RNA complexes; RRM proteins; atomistic simulations},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {Spontaneous binding of single-stranded RNAs to RRM proteins visualized by unbiased atomistic simulations with a rescaled RNA force field},
   url = {https://doi.org/10.1093/nar/gkac1106},
   volume = {50},
   year = {2022}
}

TY  - JOUR
ID  - 2248162
AU  - Krepl, Miroslav - Pokorná, Pavlína - Mlýnský, Vojtěch - Stadlbauer, Petr - Šponer, Jiří
PY  - 2022
TI  - Spontaneous binding of single-stranded RNAs to RRM proteins visualized by unbiased atomistic simulations with a rescaled RNA force field
JF  - Nucleic Acids Research
VL  - 50
IS  - 21
SP  - 12480-12496
EP  - 12480-12496
PB  - Oxford University Press
SN  - 03051048
KW  - protein/RNA complexes
KW  - RRM proteins
KW  - atomistic simulations
UR  - https://doi.org/10.1093/nar/gkac1106
N2  - Recognition of single-stranded RNA (ssRNA) by RNA recognition motif (RRM) domains is an important class of protein–RNA interactions. Many such complexes were characterized using nuclear magnetic resonance (NMR) and/or X-ray crystallography techniques, revealing ensemble-averaged pictures of the bound states. However, it is becoming widely accepted that better understanding of protein–RNA interactions would be obtained from ensemble descriptions. Indeed, earlier molecular dynamics simulations of bound states indicated visible dynamics at the RNA–RRM interfaces. Here, we report the first atomistic simulation study of spontaneous binding of short RNA sequences to RRM domains of HuR and SRSF1 proteins. Using a millisecond-scale aggregate ensemble of unbiased simulations, we were able to observe a few dozen binding events. HuR RRM3 utilizes a pre-binding state to navigate the RNA sequence to its partially disordered bound state and then to dynamically scan its different binding registers. SRSF1 RRM2 binding is more straightforward but still multiple-pathway. The present study necessitated development of a goal-specific force field modification, scaling down the intramolecular van der Waals interactions of the RNA which also improves description of the RNA–RRM bound state. Our study opens up a new avenue for large-scale atomistic investigations of binding landscapes of protein–RNA complexes, and future perspectives of such research are discussed.
ER  -

KREPL, Miroslav, Pavlína POKORNÁ, Vojtěch MLÝNSKÝ, Petr STADLBAUER and Jiří ŠPONER. Spontaneous binding of single-stranded RNAs to RRM proteins visualized by unbiased atomistic simulations with a rescaled RNA force field. \textit{Nucleic Acids Research}. Oxford University Press, 2022, vol.~50, No~21, p.~12480-12496. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkac1106.

Detailed Information on Publication Record