Dynamic Specification of Initial Structures in Parallel Cascade Selection Molecular Dynamics (PaCS-MD) Efficiently Promotes Biologically Relevant Rare Events

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Abstract

<p>Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is an enhanced conformational sampling method for generating structural transition pathways between a given reactant and a product. To promote structural transitions from the reactant to the product, PaCS-MD repeats cycles of conformational resampling of (1) reasonable initial structures and (2) short-time MD simulations restarting the structures with renewed velocities. Appropriately setting a number of these initial structures is essential for efficient PaCS-MD.</p><p>We propose a novel, optimal algorithm for specifying suitable initial structures, <i>n</i><sub>initial</sub>, to find structural transitions; this is referred to as d<i>n</i>-PaCS-MD. PaCS-MD typically has a fixed <i>n</i><sub>initial</sub>, while in d<i>n</i>-PaCS-MD it is dynamically reset according to a minimum root mean square deviation (RMSD), defined as an RMSD derivative. d<i>n</i>-PaCS-MD, with the dynamic <i>n</i><sub>initial</sub> accelerates structural transitions to the product, compared to the original PaCS-MD with the fixed <i>n</i><sub>initial</sub>, as confirmed in Chignolin protein-folding. This algorithm was also applied to Human-β-defensin 2, whose X-ray and NMR structures differ in the N-terminal region. Finally, we compared forward and backward transition pathways from the former to the latter generated by our method, and estimated a free energy barrier between them, creating new possibilities to visualize the NMR and X-ray structures in solution.</p>

Journal

  • Bulletin of the Chemical Society of Japan

    Bulletin of the Chemical Society of Japan 90(11), 1236-1243, 2017

    The Chemical Society of Japan

Codes

  • NII Article ID (NAID)
    130006201499
  • NII NACSIS-CAT ID (NCID)
    AA00580132
  • Text Lang
    ENG
  • ISSN
    0009-2673
  • NDL Article ID
    028641011
  • NDL Call No.
    Z53-B35
  • Data Source
    NDL  J-STAGE 
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