Molecular basis of Arginine and Lysine DNA sequence-dependent thermo-stability modulation

PLoS Comput Biol. 2022 Jan 10;18(1):e1009749. doi: 10.1371/journal.pcbi.1009749. eCollection 2022 Jan.


We have used a variety of theoretical and experimental techniques to study the role of four basic amino acids-Arginine, Lysine, Ornithine and L-2,4-Diaminobutyric acid-on the structure, flexibility and sequence-dependent stability of DNA. We found that the presence of organic ions stabilizes the duplexes and significantly reduces the difference in stability between AT- and GC-rich duplexes with respect to the control conditions. This suggests that these amino acids, ingredients of the primordial soup during abiogenesis, could have helped to equalize the stability of AT- and GC-rich DNA oligomers, facilitating a general non-catalysed self-replication of DNA. Experiments and simulations demonstrate that organic ions have an effect that goes beyond the general electrostatic screening, involving specific interactions along the grooves of the double helix. We conclude that organic ions, largely ignored in the DNA world, should be reconsidered as crucial structural elements far from mimics of small inorganic cations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Basic* / analysis
  • Amino Acids, Basic* / chemistry
  • Aminobutyrates / chemistry
  • Base Composition
  • Base Sequence*
  • DNA* / analysis
  • DNA* / chemistry
  • Molecular Dynamics Simulation
  • Origin of Life
  • Thermodynamics


  • Amino Acids, Basic
  • Aminobutyrates
  • 2,4-diaminobutyric acid
  • DNA

Grant support

This work was supported by the Spanish Ministry of Science [BFU2014-61670-EXP, BFU2017-89707-P] (MO), the Catalan Government [Grant 2017-SGR-134] (MO), the Instituto de Salud Carlos III–Instituto Nacional de Bioinformática (MO), the European Union's Horizon 2020 research and innovation program [676556] (MO), the Biomolecular and Bioinformatics Resources Platform [ISCIII PT 13/0001/0030 and 17/0009/0007 co-funded by the Fondo Europeo de Desarrollo Regional (FEDER)] (MO), the European Research Council [ERC SimDNA] (MO), the Ministry of Economy and Competitiveness [Elixir-Excelerate 676559 and BioExcel2 823830] (MO), and the Severo Ochoa Award of Excellence from the Government of Spain (to IRB Barcelona). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.