title: Significant strength of charged DNA-protein π-π interactions: a preliminary study of cytosine.
abstract: The present work characterized the preferred gas-phase structure and optimum interaction energy of both parallel stacked and perpendicular T-shaped dimers between cytosine (C), as a representative nucleobase, and aspartic/glutamic acid (DE), aspartate/glutamate (DE(-)) or arginine (R(+)), using detailed M06-2X/6-31+G(d,p) potential energy surface scans as a function of the relative monomer orientation. Through comparison to previous literature on the π-π interactions between the DNA nucleobases and the aromatic amino acid residues, this work will allow for comparisons between DNA-protein interactions involving aromatic and acyclic R-side chains, as well as comparisons of the relative geometric dependence and magnitude of π-π (C:DE), πcation-π (C:R(+)), and πanion-π (C:DE(-)) interactions. Our results show that the preferred relative monomer orientation is highly dependent on the monomer composition and charge, and is dictated by electrostatic-driven interactions. More importantly, for the first time, we report that the π-π interactions between cytosine and (neutral) aspartic/glutamic acid are up to approximately -40 kJ mol(-1), while the πcation-π or πanion-π interactions between cytosine and arginine or aspartate/glutamate are up to approximately -90 and -99 kJ mol(-1), respectively. An extensive investigation of the effects of the computational methodology implemented, including comparisons to detailed CCSD(T)/CBS potential energy surfaces and interaction energies, supports the use of M06-2X, as well as ωB97X-D, to study DNA-protein π-π interactions of varying composition and charge. Most importantly, the CCSD(T)/CBS results verify the strong nature of these DNA-protein π-π interactions, as well as the unique nature of the πcation-π and πanion-π counterparts. Therefore, our results emphasize that a wide variety of different types of noncovalent interactions between both cyclic and acyclic π-containing components can significantly contribute to the stability of DNA-protein complexes and likely play a larger role in biology than currently accepted.
authors.affiliation: Department of Chemistry and Biochemistry, University of Lethbridge , 4401 University Drive West, Lethbridge, Alberta, Canada T1K 3M4.
authors.forename: Rachael A
authors.initials: RA
authors.lastname: Wells
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kellie
authors.forename: Stacey D
authors.initials: SD
authors.lastname: Wetmore
mesh_terms: D001120:Arginine / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D003596:Cytosine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D018698:Glutamic Acid / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D011506:Proteins; D001224:Aspartic Acid; D018698:Glutamic Acid; D003596:Cytosine; D004247:DNA; D001120:Arginine