Abstract
For the first time novel high-energy conformers–A·T(wWC) (5.36), A·T(wrWC) (5.97), A·T(wH) (5.78), and A·T(wrH) (ΔG = 5.82 kcal·mol−1) (See Graphical ) were revealed for each of the four biologically important A·T DNA base pairs – Watson-Crick A·T(WC), reverse Watson-Crick A·T(rWC), Hoogsteen A·T(H) and reverse Hoogsteen A·T(rH) at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level of quantum-mechanical theory in the continuum with ε = 4 under normal conditions. Each of these conformers possesses substantially non-planar wobble (w) structure and is stabilized by the participation of the two anti-parallel N6H/N6H′…O4/O2 and N3H…N6 H-bonds, involving the pyramidalized amino group of the A DNA base as an acceptor and a donor of the H-bonding. The transition states – TSA·T(WC)↔A·T(wWC), TSA·T(rWC)↔A·T(wrWC), TSA·T(H)↔A·T(wH), and TSA·T(rH)↔A·T(wrH), controlling the dipole-active transformations of the conformers from the main plane-symmetric state into the high-energy, significantly non-planar state and vice versa, were localized. They also possess wobble structures similarly to the high-energy conformers and are stabilized by the participation of the N6H/N6H′…O4/O2 and N3H…N6 H-bonds. Discovered conformers of the A·T DNA base pairs are dynamically stable short-lived structures [lifetime τ = (1.4–3.9) ps]. Their possible biological significance and future perspectives have been briefly discussed.
Highlights
Investigation of the dynamics of the isolated DNA base pairs by both the experimental and especially theoretical methods is urgent biophysical task of exceptional importance (Keepers et al, 1982; Pechenaya and Volkov, 1984; Volkov, 1995; Auffinger and Westhof, 1999)
Spontaneous thermal fluctuations or breathing of DNA enables the opening of the DNA base pairs, making reactive their chemical groups, that are normally hidden inside the DNA double helix, available for hydrogen exchange involving imino and amino groups, chemical modification
That reactions of the hydrogen exchange and formaldehyde interaction with DNA were the first documented cases evidencing the opening of the DNA base pairs (Lazurkin et al, 1970; Frank-Kamenetskii and Lazurkin, 1974; Lukashin et al, 1976; Chay, 1979; Guéron et al, 1987)
Summary
Investigation of the dynamics of the isolated DNA base pairs by both the experimental and especially theoretical methods is urgent biophysical task of exceptional importance (Keepers et al, 1982; Pechenaya and Volkov, 1984; Volkov, 1995; Auffinger and Westhof, 1999). It is believed that opening of the DNA base pairs with a defined probability ∼10−5 (Lazurkin et al, 1970; FrankKamenetskii and Lazurkin, 1974; Lukashin et al, 1976; FrankKamenetskii, 1981, 1985; Guéron et al, 1987; Guéron and Leroy, 1995; von Hippel et al, 2013; Frank-Kamenetskii and Prakash, 2014) precedes the melting of DNA, that is represent the twostate model according to which each base pair is suggested to stay in the closed or open states (Frank-Kamenetskii and Lazurkin, 1974; Lukashin et al, 1976; Chay, 1979; Frank-Kamenetskii, 1981, 1983; Guéron et al, 1987; Singh and Singh, 2017) This model could quantitatively explain in details the melting of DNA processing in the multistate way due the different length and heterogeneous sequence (Vologodskii et al, 1984; Wartell and Benight, 1985; Wada and Suyama, 1986; SantaLucia, 1998). According to the literature data it remains unknown, what the nature of the open state of the DNA base pairs is and whether there is a barrier on the potential energy surface for providing its existence (Lavery, 1994; Stofer et al, 1999; Yang et al, 2015)
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