Molecular basis for the increased affinity of an RNA recognition motif with re-engineered specificity: A molecular dynamics and enhanced sampling simulations study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F18%3A73592094" target="_blank" >RIV/61989592:15310/18:73592094 - isvavai.cz</a>

Výsledek na webu

<a href="https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1006642&type=printable" target="_blank" >https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1006642&type=printable</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pcbi.1006642" target="_blank" >10.1371/journal.pcbi.1006642</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular basis for the increased affinity of an RNA recognition motif with re-engineered specificity: A molecular dynamics and enhanced sampling simulations study

Popis výsledku v původním jazyce

The RNA recognition motif (RRM) is the most common RNA binding domain across eukaryotic proteins. It is therefore of great value to engineer its specificity to target RNAs of arbitrary sequence. This was recently achieved for the RRM in Rbfox protein, where four mutations R118D, E147R, N151S, and E152T were designed to target the precursor to the oncogenic miRNA 21. Here, we used a variety of molecular dynamics-based approaches to predict specific interactions at the binding interface. Overall, we have run approximately 50 microseconds of enhanced sampling and plain molecular dynamics simulations on the engineered complex as well as on the wild-type Rbfox. pre-miRNA 20b from which the mutated systems were designed. Comparison with the available NMR data on the wild type molecules (protein, RNA, and their complex) served to establish the accuracy of the calculations.

Název v anglickém jazyce

Molecular basis for the increased affinity of an RNA recognition motif with re-engineered specificity: A molecular dynamics and enhanced sampling simulations study

Popis výsledku anglicky

The RNA recognition motif (RRM) is the most common RNA binding domain across eukaryotic proteins. It is therefore of great value to engineer its specificity to target RNAs of arbitrary sequence. This was recently achieved for the RRM in Rbfox protein, where four mutations R118D, E147R, N151S, and E152T were designed to target the precursor to the oncogenic miRNA 21. Here, we used a variety of molecular dynamics-based approaches to predict specific interactions at the binding interface. Overall, we have run approximately 50 microseconds of enhanced sampling and plain molecular dynamics simulations on the engineered complex as well as on the wild-type Rbfox. pre-miRNA 20b from which the mutated systems were designed. Comparison with the available NMR data on the wild type molecules (protein, RNA, and their complex) served to establish the accuracy of the calculations.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/LO1305" target="_blank" >LO1305: Rozvoj centra pokročilých technologií a materiálů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

PLoS Computational Biology

ISSN

1553-734X

e-ISSN

—

Svazek periodika

14

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

27

Strana od-do

"e1006642-1"-"e1006642-27"

Kód UT WoS článku

000454835100039

EID výsledku v databázi Scopus

2-s2.0-85059242857