Unravelling Protein–DNA Interactions at Molecular Level: A DFT and NCI Study

  1. González, J. 3
  2. Baños, I. 2
  3. León, I. 3
  4. Contreras-García, J. 15
  5. Cocinero, E.J. 3
  6. Lesarri, A. 4
  7. Fernández, J.A. 3
  8. Millán, J. 2
  1. 1 Centre National de la Recherche Scientifique
    info

    Centre National de la Recherche Scientifique

    París, Francia

    ROR https://ror.org/02feahw73

  2. 2 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  3. 3 Universidad del País Vasco/Euskal Herriko Unibertsitatea
    info

    Universidad del País Vasco/Euskal Herriko Unibertsitatea

    Lejona, España

    ROR https://ror.org/000xsnr85

  4. 4 Universidad de Valladolid
    info

    Universidad de Valladolid

    Valladolid, España

    ROR https://ror.org/01fvbaw18

  5. 5 Sorbonne Universités
    info

    Sorbonne Universités

    París, Francia

    ROR https://ror.org/02en5vm52

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Revista:
Journal of Chemical Theory and Computation

ISSN: 1549-9618

Ano de publicación: 2016

Volume: 12

Número: 2

Páxinas: 523-534

Tipo: Artigo

SCOPUS: 2-s2.0-84957949710 WoS: WOS:000370112900007 GOOGLE SCHOLAR

Outras publicacións en: Journal of Chemical Theory and Computation

Resumo

Histone–DNA interactions were probed computationally at a molecular level, by characterizing the bimolecular clusters constituted by selected amino acid derivatives with polar (asparagine and glutamine), nonpolar (alanine, valine, and isoleucine), and charged (arginine) side chains and methylated pyrimidinic (1-methylcytosine and 1-methylthymine) and puric (9-methyladenine and 9-methylguanine) DNA bases. The computational approach combined different methodologies: a molecular mechanics (MMFFs forced field) conformational search and structural and vibrational density-functional calculations (M06-2X with double and triple-ζ Pople’s basis sets). To dissect the interactions, intermolecular forces were analyzed with the Non-Covalent Interactions (NCI) analysis. The results for the 24 different clusters studied show a noticeable correlation between the calculated binding energies and the propensities for protein–DNA base interactions found in the literature. Such correlation holded even for the interaction of the selected amino acid derivatives with Watson and Crick pairs. Therefore, the balance between hydrogen bonds and van der Waals interactions (specially stacking) in the control of the final shape of the investigated amino acid–DNA base pairs seems to be well reproduced in dispersion-corrected DFT molecular models, reinforcing the idea that the specificity between the amino acids and the DNA bases play an important role in the regulation of DNA