Elucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches

Handle URI:
http://hdl.handle.net/10754/622141
Title:
Elucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches
Authors:
Jiang, Hanlun; Zhu, Lizhe; Héliou, Amélie; Gao, Xin ( 0000-0002-7108-3574 ) ; Bernauer, Julie; Huang, Xuhui
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.
KAUST Department:
Computational Bioscience Research Center (CBRC); Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Jiang H, Zhu L, Héliou A, Gao X, Bernauer J, et al. (2016) Elucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches. Drug Target miRNA: 251–275. Available: http://dx.doi.org/10.1007/978-1-4939-6563-2_18.
Publisher:
Springer Nature
Journal:
Methods in Molecular Biology
Issue Date:
6-Dec-2016
DOI:
10.1007/978-1-4939-6563-2_18
Type:
Book Chapter
ISSN:
1064-3745; 1940-6029
Sponsors:
This work is supported by the Hong Kong Research Grant Council [grant numbers 16302214, 609813, HKUST C6009-15G, AoE/ M-09/12, M-HKUST601/13, and T13-607/12R to X.H.] and the National Science Foundation of China [grant number 21273188 to X.H.]. The work is also supported by a grant from the PROCOREFrance/ Hong Kong Joint Research Scheme sponsored by the Research Grants Council and the Consulate General of France in Hong Kong (F-HK29/11T) (X.H. and J.B.). X.G. was supported by funding from King Abdullah University of Science and Technology. This research made use of the resources of the Supercomputing Laboratory at King Abdullah University of Science and Technology.
Additional Links:
http://link.springer.com/protocol/10.1007%2F978-1-4939-6563-2_18
Appears in Collections:
Computational Bioscience Research Center (CBRC); Book Chapters; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorJiang, Hanlunen
dc.contributor.authorZhu, Lizheen
dc.contributor.authorHéliou, Amélieen
dc.contributor.authorGao, Xinen
dc.contributor.authorBernauer, Julieen
dc.contributor.authorHuang, Xuhuien
dc.date.accessioned2017-01-02T08:10:21Z-
dc.date.available2017-01-02T08:10:21Z-
dc.date.issued2016-12-06en
dc.identifier.citationJiang H, Zhu L, Héliou A, Gao X, Bernauer J, et al. (2016) Elucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches. Drug Target miRNA: 251–275. Available: http://dx.doi.org/10.1007/978-1-4939-6563-2_18.en
dc.identifier.issn1064-3745en
dc.identifier.issn1940-6029en
dc.identifier.doi10.1007/978-1-4939-6563-2_18en
dc.identifier.urihttp://hdl.handle.net/10754/622141-
dc.description.abstractMicroRNA (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.en
dc.description.sponsorshipThis work is supported by the Hong Kong Research Grant Council [grant numbers 16302214, 609813, HKUST C6009-15G, AoE/ M-09/12, M-HKUST601/13, and T13-607/12R to X.H.] and the National Science Foundation of China [grant number 21273188 to X.H.]. The work is also supported by a grant from the PROCOREFrance/ Hong Kong Joint Research Scheme sponsored by the Research Grants Council and the Consulate General of France in Hong Kong (F-HK29/11T) (X.H. and J.B.). X.G. was supported by funding from King Abdullah University of Science and Technology. This research made use of the resources of the Supercomputing Laboratory at King Abdullah University of Science and Technology.en
dc.publisherSpringer Natureen
dc.relation.urlhttp://link.springer.com/protocol/10.1007%2F978-1-4939-6563-2_18en
dc.subjectArgonauteen
dc.subjectMarkov state modelen
dc.subjectmiRNAen
dc.subjectMolecular dynamicsen
dc.subjectMolecular recognitionen
dc.subjectProtein-RNA dockingen
dc.titleElucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approachesen
dc.typeBook Chapteren
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalMethods in Molecular Biologyen
dc.contributor.institutionStructure and Design, University of Washington, Seattle, WA, 98195, United Statesen
dc.contributor.institutionDepartment of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kongen
dc.contributor.institutionCenter of Systems Biology and Human Health, School of Science and Institute for Advance Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Chinaen
dc.contributor.institutionInria Saclay-Île de France, École Polytechnique, 1 rue Honoré d’Estienne d’Orves, Bâtiment Alan Turing Campus de l’, Palaiseau, 91120, Franceen
dc.contributor.institutionLaboratoire d’Informatique de l’École Polytechnique (LIX), CNRS UMR 7161, École Polytechnique, Palaiseau, 91128, Franceen
dc.contributor.institutionDivision of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kongen
kaust.authorGao, Xinen
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