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Free-Energy Landscape of Intrinsically Disordered Proteins Investigated by All-Atom Multicanonical Molecular Dynamics

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Protein Conformational Dynamics

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 805))

Abstract

We introduce computational studies on intrinsically disordered proteins (IDPs). Especially, we present our multicanonical molecular dynamics (McMD) simulations of two IDP-partner systems: NRSF–mSin3 and pKID–KIX. McMD is one of enhanced conformational sampling methods useful for conformational sampling of biomolecular systems. IDP adopts a specific tertiary structure upon binding to its partner molecule, although it is unstructured in the unbound state (i.e. the free state). This IDP-specific property is called “coupled folding and binding”. The McMD simulation treats the biomolecules with an all-atom model immersed in an explicit solvent. In the initial configuration of simulation, IDP and its partner molecules are set to be distant from each other, and the IDP conformation is disordered. The computationally obtained free-energy landscape for coupled folding and binding has shown that native- and non-native-complex clusters distribute complicatedly in the conformational space. The all-atom simulation suggests that both of induced-folding and population-selection are coupled complicatedly in the coupled folding and binding. Further analyses have exemplified that the conformational fluctuations (dynamical flexibility) in the bound and unbound states are essentially important to characterize IDP functioning.

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Acknowledgements

Both authors were supported by a Grant-in-Aid for Scientific Research on Innovative Areas (21113006) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan. J.H. was supported by grants from the New Energy and Industrial Technology Development Organization (NEDO) Japan.

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Authors and Affiliations

  1. Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Junichi Higo

  2. Graduate School of Advanced Science and Engineering, Waseda University, Okubo 3-4-1, Shinjuku-Ku, Tokyo, 169-8555, Japan

    Koji Umezawa

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  1. Junichi Higo
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  2. Koji Umezawa
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Correspondence to Junichi Higo .

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Editors and Affiliations

  1. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China

    Ke-li Han

  2. The Scripps Research Institute, La Jolla, California, USA

    Xin Zhang

  3. Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People's Republic of China

    Ming-jun Yang

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Higo, J., Umezawa, K. (2014). Free-Energy Landscape of Intrinsically Disordered Proteins Investigated by All-Atom Multicanonical Molecular Dynamics. In: Han, Kl., Zhang, X., Yang, Mj. (eds) Protein Conformational Dynamics. Advances in Experimental Medicine and Biology, vol 805. Springer, Cham. https://doi.org/10.1007/978-3-319-02970-2_14

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