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Free Energy Surface of an Intrinsically Disordered Protein: Comparison between Temperature Replica Exchange Molecular Dynamics and Bias-Exchange Metadynamics
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    Free Energy Surface of an Intrinsically Disordered Protein: Comparison between Temperature Replica Exchange Molecular Dynamics and Bias-Exchange Metadynamics
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    Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, United States
    Institute of Computational and Molecular Science, Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, United States
    *E-mail: [email protected]. (D.G.)
    *E-mail: [email protected]. (J.M.)
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    Journal of Chemical Theory and Computation

    Cite this: J. Chem. Theory Comput. 2015, 11, 6, 2776–2782
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    https://doi.org/10.1021/acs.jctc.5b00047
    Published April 28, 2015
    Copyright © 2015 American Chemical Society

    Abstract

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    Intrinsically disordered proteins (IDPs), which are expected to be largely unstructured under physiological conditions, make up a large fraction of eukaryotic proteins. Molecular dynamics simulations have been utilized to probe structural characteristics of these proteins, which are not always easily accessible to experiments. However, exploration of the conformational space by brute force molecular dynamics simulations is often limited by short time scales. Present literature provides a number of enhanced sampling methods to explore protein conformational space in molecular simulations more efficiently. In this work, we present a comparison of two enhanced sampling methods: temperature replica exchange molecular dynamics and bias exchange metadynamics. By investigating both the free energy landscape as a function of pertinent order parameters and the per-residue secondary structures of an IDP, namely, human islet amyloid polypeptide, we found that the two methods yield similar results as expected. We also highlight the practical difference between the two methods by describing the path that we followed to obtain both sets of data.

    Copyright © 2015 American Chemical Society

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    Detailed equations describing collective variables and parameters for equations and metadynamics calculations, as well as ranges and bin sizes for the free energy reconstruction of BEMD and PMF calculations of T-REMD and the neutral replica of BEMD. The free energy projected on the α-RMSD CV for the initial benchmark run of hIAPP and free energies projected on each collective variable and secondary structures obtained from T-REMD, reweighted BEMD, and the neutral replica of BEMD. This material is available free of charge via the Internet at http://pubs.acs.org/.The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jctc.5b00047.

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    Journal of Chemical Theory and Computation

    Cite this: J. Chem. Theory Comput. 2015, 11, 6, 2776–2782
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jctc.5b00047
    Published April 28, 2015
    Copyright © 2015 American Chemical Society

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