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

dc.contributor.authorJiang, Hanlun
dc.contributor.authorZhu, Lizhe
dc.contributor.authorHéliou, Amélie
dc.contributor.authorGao, Xin
dc.contributor.authorBernauer, Julie
dc.contributor.authorHuang, Xuhui
dc.date.accessioned2017-01-02T08:10:21Z
dc.date.available2017-01-02T08:10:21Z
dc.date.issued2016-12-07
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.
dc.identifier.issn1064-3745
dc.identifier.issn1940-6029
dc.identifier.doi10.1007/978-1-4939-6563-2_18
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.
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.
dc.publisherSpringer Nature
dc.relation.urlhttp://link.springer.com/protocol/10.1007%2F978-1-4939-6563-2_18
dc.subjectArgonaute
dc.subjectMarkov state model
dc.subjectmiRNA
dc.subjectMolecular dynamics
dc.subjectMolecular recognition
dc.subjectProtein-RNA docking
dc.titleElucidating Mechanisms of Molecular Recognition Between Human Argonaute and miRNA Using Computational Approaches
dc.typeBook Chapter
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.contributor.departmentComputer Science Program
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
dc.identifier.journalMethods in Molecular Biology
dc.contributor.institutionStructure and Design, University of Washington, Seattle, WA, 98195, United States
dc.contributor.institutionDepartment of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong
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, China
dc.contributor.institutionInria Saclay-Île de France, École Polytechnique, 1 rue Honoré d’Estienne d’Orves, Bâtiment Alan Turing Campus de l’, Palaiseau, 91120, France
dc.contributor.institutionLaboratoire d’Informatique de l’École Polytechnique (LIX), CNRS UMR 7161, École Polytechnique, Palaiseau, 91128, France
dc.contributor.institutionDivision of Biomedical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong
kaust.personGao, Xin
dc.date.published-online2016-12-07
dc.date.published-print2017


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