Sampling of near-native protein conformations during protein structure refinement using a coarse-grained model, normal modes, and molecular dynamics simulations

Authors

  • Andrew W. Stumpff-Kane,

    1. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824-1319
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  • Katarzyna Maksimiak,

    1. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824-1319
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  • Michael S. Lee,

    1. Computational Sciences and Engineering Branch, United States Army Research Laboratory, Aberdeen Proving Ground, Aberdeen, Maryland 21005
    2. Department of Cell Biology and Biochemistry, United States Army Medical Research Institute for Infectious Diseases, Frederick, Maryland 21702-5011
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  • Michael Feig

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824-1319
    2. Department of Chemistry, Michigan State University, East Lansing, Michigan 48824-1319
    • Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319
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Abstract

Protein structure refinement from comparative models with the goal of predicting structures at near-experimental accuracy remains an unsolved problem. Structure refinement might be achieved with an iterative protocol where the most native-like structure from a set of decoys generated from an initial model in one cycle is used as the starting structure for the next cycle. Conformational sampling based on the coarse-grained SICHO model, atomic level of detail molecular dynamics simulations, and normal-mode analysis is compared in the context of such a protocol. All of the sampling methods can achieve significant refinement close to experimental structures, although the distribution of structures and the ability to reach native-like structures differs greatly. Implications for the practical application of such sampling methods and the requirements for scoring functions in an iterative refinement protocol are analyzed in the context of theoretical predictions for the distribution of protein-like conformations with a random sampling protocol. Proteins 2008. © 2007 Wiley-Liss, Inc.

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