Twist, grind, translocate: pepper-mill dynamics of MSPA protein pore during ssDNA transport

Priya Dey1, Brandon Meza-González1, Ganesh N Pandian1

  • 1Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto 606-8501, Japan. dpackwood@icems.kyoto-u.ac.jp.

Insights

We discovered a novel "pepper-mill" motion in Mycobacterium smegmatis porin A (MSPA) during DNA translocation. This finding advances understanding of nanopore sensing and DNA sequencing technologies.

Area of Science:

  • Biophysics
  • Computational Biology
  • Nanotechnology

Background:

  • DNA translocation through protein nanopores is vital for biological processes and DNA sequencing.
  • Mycobacterium smegmatis porin A (MSPA) is a promising nanopore for single-molecule sensing due to its structure.
  • The atomic-level mechanism of DNA interaction with MSPA's dynamic motions is not well understood.

Purpose of the Study:

  • To elucidate the mechanism of single-stranded DNA (ssDNA) translocation through the MSPA nanopore.
  • To investigate the coupling between DNA and the dynamic motions of the MSPA pore at the atomic scale.

Main Methods:

  • Atomistic molecular dynamics (MD) simulations.
  • Dimensionality reduction techniques.
  • Cross-correlation analyses of simulation data.

Main Results:

  • A previously unidentified "pepper-mill"-like motion of MSPA was observed during ssDNA translocation.
  • This collective domain motion significantly influences analyte-pore interactions and DNA passage dynamics.
  • A generalizable, data-driven strategy was developed for extracting mechanistic insights from complex biomolecular simulations.

Conclusions:

  • The identified MSPA motion is critical for regulating DNA translocation.
  • Data-driven computational approaches can provide valuable insights for nanopore engineering.
  • This work accelerates the development of advanced DNA sequencing and biosensing technologies.

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