ArticlePLoS computational biology2015
Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed.
- A continuous-space analytical framework for committor functions from molecular dynamics.The Journal of chemical physics · 2026Article
- The miRNA Landscape of Leukemia - Cellular Actions to Therapy through Molecular Mechanisms.Cell biochemistry and biophysics · 2025Review
- Conformational Dynamics of hAgo2 Silencing: Decoding Functional Divergence across Human Argonaute Paralogs.Journal of chemical information and modeling · 2025Article
- AMUSET-TICA: A Tensor-Based Approach for Identifying Slow Collective Variables in Biomolecular Dynamics.Journal of chemical theory and computation · 2025Article
- Unveiling the Conformational Dynamics of the Histone Tails Using Markov State Modeling.Journal of chemical theory and computation · 2025Article
- Exploring transition states of protein conformational changes via out-of-distribution detection in the hyperspherical latent space.Nature communications · 2025Article
- Non-Markovian Dynamic Models Identify Non-Canonical KRAS-VHL Encounter Complex Conformations for Novel PROTAC Design.JACS Au · 2024Article
- Tutorial on how to build non-Markovian dynamic models from molecular dynamics simulations for studying protein conformational changes.The Journal of chemical physics · 2024Article
- Integrative generalized master equation: A method to study long-timescale biomolecular dynamics via the integrals of memory kernels.The Journal of chemical physics · 2023Article
- GraphVAMPnets for uncovering slow collective variables of self-assembly dynamics.The Journal of chemical physics · 2023Article
- An Efficient Path Classification Algorithm Based on Variational Autoencoder to Identify Metastable Path Channels for Complex Conformational Changes.Journal of chemical theory and computation · 2023Article
- Disease mutations and phosphorylation alter the allosteric pathways involved in autoinhibition of protein phosphatase 2A.The Journal of chemical physics · 2023Article
- RNA-protein complexes and force field polarizability.Frontiers in chemistry · 2023Article
- Mechanistic Insights into the Protection Effect of Argonaute-RNA Complex on the HCV Genome.Biomolecules · 2022Article
- Elucidation of the conformational dynamics and assembly of Argonaute-RNA complexes by distinct yet coordinated actions of the supplementary microRNA.Computational and structural biotechnology journal · 2022Article
- 3D Modeling of Non-coding RNA Interactions.Advances in experimental medicine and biology · 2022Article
- Critical role of backbone coordination in the mRNA recognition by RNA induced silencing complex.Communications biology · 2021Article
- Binding-induced functional-domain motions in the Argonaute characterized by adaptive advanced sampling.PLoS computational biology · 2021Article
- Markov State Models to Study the Functional Dynamics of Proteins in the Wake of Machine Learning.JACS Au · 2021Review
- Role of bacterial RNA polymerase gate opening dynamics in DNA loading and antibiotics inhibition elucidated by quasi-Markov State Model.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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6 authors.
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Abstract
Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. In this study, we propose a two-step mechanism for this molecular recognition: selective binding followed by structural re-arrangement. Our model is based on the results of a combination of Markov State Models (MSMs), large-scale protein-RNA docking, and molecular dynamics (MD) simulations. Using MSMs, we identify an open state of apo human Ago-2 in fast equilibrium with partially open and closed states. Conformations in this open state are distinguished by their largely exposed binding grooves that can geometrically accommodate miRNA as indicated in our protein-RNA docking studies. miRNA may then selectively bind to these open conformations. Upon the initial binding, the complex may perform further structural re-arrangement as shown in our MD simulations and eventually reach the stable binary complex structure. Our results provide novel insights in Ago-miRNA recognition mechanisms and our methodology holds great potential to be widely applied in the studies of other important molecular recognition systems.
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