Bio-Inspired Models of Network, Information, and Computing Systems. 5th International ICST Conference, BIONETICS 2010, Boston, USA, December 1-3, 2010, Revised Selected Papers

Research Article

Enhancing Sampling of the Conformational Space Near the Protein Native State

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  • @INPROCEEDINGS{10.1007/978-3-642-32615-8_26,
        author={Brian Olson and Kevin Molloy and Amarda Shehu},
        title={Enhancing Sampling of the Conformational Space Near the Protein Native State},
        proceedings={Bio-Inspired Models of Network, Information, and Computing Systems. 5th International ICST Conference, BIONETICS 2010, Boston, USA, December 1-3, 2010, Revised Selected Papers},
        proceedings_a={BIONETICS},
        year={2012},
        month={10},
        keywords={protein native state conformational ensemble probabilistic search tree-based projection-guided exploration fragment library},
        doi={10.1007/978-3-642-32615-8_26}
    }
    
  • Brian Olson
    Kevin Molloy
    Amarda Shehu
    Year: 2012
    Enhancing Sampling of the Conformational Space Near the Protein Native State
    BIONETICS
    Springer
    DOI: 10.1007/978-3-642-32615-8_26
Brian Olson1, Kevin Molloy1, Amarda Shehu
  • 1: George Mason University

Abstract

A protein molecule assumes specific conformations under native conditions to fit and interact with other molecules. Due to the role that three-dimensional structure plays in protein function, significant efforts are devoted to elucidating native conformations. Many search algorithms are proposed to navigate the high-dimensional protein conformational space and its underlying energy surface in search of low-energy conformations that comprise the native state. In this work, we identify two strategies to enhance the sampling of native conformations. We show that employing an enhanced fragment library with greater structural diversity to assemble low-energy conformations allows sampling more native conformations. To efficiently handle the ensuing vast conformational space, only a representative subset of the sampled conformations are maintained and employed to further guide the search for native conformations. Our results show that these two strategies greatly enhance the sampling of the conformational space near the native state.