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    Discrete Molecular Dynamics Approach to the Study of Disordered and Aggregating Proteins
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    † Institute for Research in Biomedicine (IRB) Barcelona, The Barcelona Institute of Science and Technology, Parc Científic de Barcelona, Josep Samitier 1-5, Barcelona 08028, Spain
    ‡ Joint IRB-BSC Program on Computational Biology, Barcelona 08028, Spain
    § Departament de Bioquímica i Biomedicina, Facultat de Biología, Universitat de Barcelona, Avgda Diagonal 647, Barcelona 08028, Spain
    *E-mail: [email protected] (A.E.).
    *E-mail: [email protected] (M.O.).
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    Journal of Chemical Theory and Computation

    Cite this: J. Chem. Theory Comput. 2017, 13, 3, 1454–1461
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    https://doi.org/10.1021/acs.jctc.6b01153
    Published February 3, 2017
    Copyright © 2017 American Chemical Society
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    Abstract

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    We present a refinement of the Coarse Grained PACSAB force field for Discrete Molecular Dynamics (DMD) simulations of proteins in aqueous conditions. As the original version, the refined method provides good representation of the structure and dynamics of folded proteins but provides much better representations of a variety of unfolded proteins, including some very large, impossible to analyze by atomistic simulation methods. The PACSAB/DMD method also reproduces accurately aggregation properties, providing good pictures of the structural ensembles of proteins showing a folded core and an intrinsically disordered region. The combination of accuracy and speed makes the method presented here a good alternative for the exploration of unstructured protein systems.

    Copyright © 2017 American Chemical Society

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jctc.6b01153.

    • Table showing the RMSD of the proteins in the benchmark, ordered by sequence length; radius of gyration of ACTR using different parametrizations of the force field; RMSD obtained in the simulations of proteins in the PRIMO and OPEP benchmarks; illustration of a reversible binding event; RMSD obtained in the eight simulations of α-synuclein; mean value of the inter-residue distance as a function of the sequence separation for α-synuclein and tau; percentage of helical structure along sequence for the tau protein (PDF)

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    Cited By

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    Journal of Chemical Theory and Computation

    Cite this: J. Chem. Theory Comput. 2017, 13, 3, 1454–1461
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jctc.6b01153
    Published February 3, 2017
    Copyright © 2017 American Chemical Society
    Request reuse permissions

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