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Modeling and Simulation of the NMDA Receptor at Coarse-Grained and Atomistic Levels

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NMDA Receptors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2799))

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Abstract

N-Methyl-D-aspartate (NMDA) receptors are glutamate-gated excitatory channels that play essential roles in brain functions. While high-resolution structures were solved for an allosterically inhibited form of functional NMDA receptor, other key functional states (particularly the active open-channel state) have not yet been resolved at atomic resolutions. To decrypt the molecular mechanism of the NMDA receptor activation, structural modeling and simulation are instrumental in providing detailed information about the dynamics and energetics of the receptor in various functional states. In this chapter, we describe coarse-grained modeling of the NMDA receptor using an elastic network model and related modeling/analysis tools (e.g., normal mode analysis, flexibility and hotspot analysis, cryo-EM flexible fitting, and transition pathway modeling) based on available structures. Additionally, we show how to build an atomistic model of the active-state receptor with targeted molecular dynamics (MD) simulation and explore its energetics and dynamics with conventional MD simulation. Taken together, these modeling and simulation can offer rich structural and dynamic information which will guide experimental studies of the activation of this key receptor.

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Authors and Affiliations

  1. Department of Physics, State University of New York at Buffalo, Buffalo, NY, USA

    Wenjun Zheng & Xing Liu

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  1. Wenjun Zheng
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  2. Xing Liu
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Correspondence to Wenjun Zheng .

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Editors and Affiliations

  1. INSERM, Aix-Marseille University, Mediterranean Institute of Neurobiology (INMED), Marseille, France

    Nail Burnashev

  2. INSERM, Aix-Marseille University, Mediterranean Institute of Neurobiology (INMED), Marseille, France

    Pierre Szepetowski

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Zheng, W., Liu, X. (2024). Modeling and Simulation of the NMDA Receptor at Coarse-Grained and Atomistic Levels. In: Burnashev, N., Szepetowski, P. (eds) NMDA Receptors. Methods in Molecular Biology, vol 2799. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3830-9_15

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  • DOI: https://doi.org/10.1007/978-1-0716-3830-9_15

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3829-3

  • Online ISBN: 978-1-0716-3830-9

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