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Nucleic acid base pair open states by hydrogen exchange.

S Walter Englander1

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|December 30, 2025
PubMed
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Native DNA and RNA base pairs exhibit two distinct opening modes, revealed by hydrogen exchange (HX) experiments. These findings resolve conflicting data on nucleic acid dynamics and suggest soliton-like mechanisms for sequence exposure.

Keywords:
DNA dynamicsbase pair openinghydrogen exchangesolitons

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Area of Science:

  • Molecular Biology
  • Biophysics
  • Structural Dynamics

Background:

  • Understanding spontaneous base pair opening in native nucleic acids is crucial but remains unclear.
  • Existing hydrogen exchange (HX) studies yield contradictory data on nucleic acid structural dynamics.
  • Discrepant datasets arise from different experimental methods and molecular models used.

Purpose of the Study:

  • To reexamine existing hydrogen exchange (HX) data.
  • To resolve long-standing contradictory views on nucleic acid structural dynamics.
  • To elucidate the spontaneous base pair opening behavior of native duplexes.

Main Methods:

  • Hydrogen exchange (HX) experiments were reanalyzed.
  • Kinetic and equilibrium parameters of base pair opening reactions were measured.
  • Data from different experimental approaches (e.g., H-T exchange, H-H exchange via NMR relaxation) were compared.

Main Results:

  • Two distinct modes of base pair opening were identified, selectively accessed by different methods.
  • Large, multi-base-pair openings (milliseconds, high population) dominate HX in DNA, RNA, and long duplexes.
  • Small, single base-pair openings (microseconds, low population) dominate HX in small oligonucleotides.

Conclusions:

  • Contradictory HX datasets reflect two different base pair opening modes.
  • Methodological and size limitations explain the selective observation of these modes.
  • Observed openings suggest soliton-like wave packets dynamically scanning DNA for recognition sites.