Elucidating mechanisms of molecular recognition between human argonaute and miRNA using computational approaches

Hanlun Jiang; Lizhe Zhu; Amélie Héliou; Xin Gao; Julie Bernauer; Xuhui Huang

doi:10.1007/978-1-4939-6563-2_18

Elucidating mechanisms of molecular recognition between human argonaute and miRNA using computational approaches

Hanlun Jiang
, Lizhe Zhu
, Amélie Héliou
, Xin Gao^*
, Julie Bernauer
, Xuhui Huang

^*Corresponding author for this work

Department of Chemical and Biological Engineering

Research output: Chapter in Book/Conference Proceeding/Report › Book Chapter › peer-review

3 Citations (Scopus)

Abstract

MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition. Constructed from MD simulations, MSMs can elucidate the conformational dynamics of AGO at biologically relevant timescales. Protein-RNA docking can then efficiently identify the AGO conformations that are geometrically accessible to miRNA. Using our recent work on human AGO2 as an example, we explain the rationale and the workflow of our method in details. This combined approach holds great promise to complement experiments in unraveling the mechanisms of molecular recognition between large, flexible, and complex biomolecules.

Original language	English
Title of host publication	Methods in Molecular Biology
Publisher	Humana Press Inc.
Pages	251-275
Number of pages	25
DOIs	https://doi.org/10.1007/978-1-4939-6563-2_18
Publication status	Published - 2017

Publication series

Name	Methods in Molecular Biology
Volume	1517
ISSN (Print)	1064-3745

Bibliographical note

Publisher Copyright:
© Springer Science+Business Media New York 2017.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Argonaute
Markov state model
Molecular dynamics
Molecular recognition
Protein-RNA docking
miRNA

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10.1007/978-1-4939-6563-2_18

Cite this

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title = "Elucidating mechanisms of molecular recognition between human argonaute and miRNA using computational approaches",

abstract = "MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition. Constructed from MD simulations, MSMs can elucidate the conformational dynamics of AGO at biologically relevant timescales. Protein-RNA docking can then efficiently identify the AGO conformations that are geometrically accessible to miRNA. Using our recent work on human AGO2 as an example, we explain the rationale and the workflow of our method in details. This combined approach holds great promise to complement experiments in unraveling the mechanisms of molecular recognition between large, flexible, and complex biomolecules.",

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T1 - Elucidating mechanisms of molecular recognition between human argonaute and miRNA using computational approaches

AU - Jiang, Hanlun

AU - Zhu, Lizhe

AU - Héliou, Amélie

AU - Gao, Xin

AU - Bernauer, Julie

AU - Huang, Xuhui

N1 - Publisher Copyright: © Springer Science+Business Media New York 2017.

PY - 2017

Y1 - 2017

N2 - MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition. Constructed from MD simulations, MSMs can elucidate the conformational dynamics of AGO at biologically relevant timescales. Protein-RNA docking can then efficiently identify the AGO conformations that are geometrically accessible to miRNA. Using our recent work on human AGO2 as an example, we explain the rationale and the workflow of our method in details. This combined approach holds great promise to complement experiments in unraveling the mechanisms of molecular recognition between large, flexible, and complex biomolecules.

AB - MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition. Constructed from MD simulations, MSMs can elucidate the conformational dynamics of AGO at biologically relevant timescales. Protein-RNA docking can then efficiently identify the AGO conformations that are geometrically accessible to miRNA. Using our recent work on human AGO2 as an example, we explain the rationale and the workflow of our method in details. This combined approach holds great promise to complement experiments in unraveling the mechanisms of molecular recognition between large, flexible, and complex biomolecules.

KW - Argonaute

KW - Markov state model

KW - Molecular dynamics

KW - Molecular recognition

KW - Protein-RNA docking

KW - miRNA

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M3 - Book Chapter

T3 - Methods in Molecular Biology

SP - 251

EP - 275

BT - Methods in Molecular Biology

PB - Humana Press Inc.

ER -

Elucidating mechanisms of molecular recognition between human argonaute and miRNA using computational approaches

Abstract

Publication series

Bibliographical note

UN SDGs

Keywords

Access to Document

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