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Refinement of Generalized Born Implicit Solvation Parameters for Nucleic Acids and Their Complexes with Proteins
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    Refinement of Generalized Born Implicit Solvation Parameters for Nucleic Acids and Their Complexes with Proteins
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    † ‡ Department of Chemistry, Laufer Center for Physical and Quantitative Biology, and §Department of Biochemistry, Stony Brook University, Stony Brook, New York 11794, USA
    *(C.S.) E-mail: [email protected]
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    Journal of Chemical Theory and Computation

    Cite this: J. Chem. Theory Comput. 2015, 11, 8, 3714–3728
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    https://doi.org/10.1021/acs.jctc.5b00271
    Published July 7, 2015
    Copyright © 2015 American Chemical Society

    Abstract

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    The Generalized Born (GB) implicit solvent model has undergone significant improvements in accuracy for modeling of proteins and small molecules. However, GB still remains a less widely explored option for nucleic acid simulations, in part because fast GB models are often unable to maintain stable nucleic acid structures or they introduce structural bias in proteins, leading to difficulty in application of GB models in simulations of protein–nucleic acid complexes. Recently, GB-neck2 was developed to improve the behavior of protein simulations. In an effort to create a more accurate model for nucleic acids, a similar procedure to the development of GB-neck2 is described here for nucleic acids. The resulting parameter set significantly reduces absolute and relative energy error relative to Poisson–Boltzmann for both nucleic acids and nucleic acid–protein complexes, when compared to its predecessor GB-neck model. This improvement in solvation energy calculation translates to increased structural stability for simulations of DNA and RNA duplexes, quadruplexes, and protein–nucleic acid complexes. The GB-neck2 model also enables successful folding of small DNA and RNA hairpins to near native structures as determined from comparison with experiment. The functional form and all required parameters are provided here and also implemented in the AMBER software.

    Copyright © 2015 American Chemical Society

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    Supporting Information

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    Tables of training results, summaries of DNA, RNA, and protein/DNA complex systems used in this study, table of large errors for effective radii for original GB-neck model, and tables of major and minor groove width for various DNA and RNA systems. Figures of comparison between GB and PB calculation (perfect radii, energies) for various systems, figures of backbone RMSD vs time for various systems. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jctc.5b00271.

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    Journal of Chemical Theory and Computation

    Cite this: J. Chem. Theory Comput. 2015, 11, 8, 3714–3728
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jctc.5b00271
    Published July 7, 2015
    Copyright © 2015 American Chemical Society

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