Interaction of 2′-Deoxyadenosine with <i>cis</i>-2-Butene-1,4-dial: Computational Approach to Analysis of Multistep Chemical Reactions

The computational analysis of multistep chemical interactions between 2′-deoxyadenosine and <i>cis</i>-2-butene-1,4-dial has been performed. The applied protocol includes generation of a multistep Gibbs free-energy reaction profile (PCM/M05-2X/6-311+G­(d) level) for the transformations of the reagents to products, followed by evaluation of the rate constants, construction of the corresponding kinetic equations, and solving them. Such a procedure allows one to significantly extend the number of experimentally determined steps by addition of the ones computationally predicted. The primary products of the reaction are found to be four diastereomeric adducts characterized by virtually the same stability. The acid-catalyzed dehydration of these adducts leads to a more stable secondary product. Computational verification of UV and NMR spectra has also been performed. It has been revealed that simulated UV and NMR spectra of primary and secondary 2′-deoxyadenosine adducts of <i>cis</i>-2-butene-1,4-dial are in agreement with the experimental observations

Structural Waters in the Minor and Major Grooves of DNAA Major Factor Governing Structural Adjustments of the A–T Mini-Helix

The role of microhydration in structural adjustments of the AT-tract in B-DNA was studied at the B97-D/def2-SV­(P) level. The (dA:dT)₅ complexes with 10 water molecules in minor and 15 water molecules in major grooves were studied. The obtained network of hydrogen bonds revealed the dependence between the groove width and the types of water patterns. In the minor groove, the following patterns were observed: interstrand one-water bridges similar to that of the Dickerson “water spine” and interstrand two-water bridges. The network of structural waters in the major groove is more diverse than that in the minor groove, which agrees with crystallographic data. As the major groove is wider, it is enriched by water molecules forming two- and three-water bridges. Results suggest the nucleobase–water interactions in both grooves prevent AT-tract twisting and its “collapse” along the minor groove. Whereby, a helix structure with narrow minor and wide major grooves is formed. The structural waters affect the polynucleotide conformation so that it becomes similar to poly­(dA)·poly­(dT) in fibers and acquires features of the A-tracts in DNA in solution. We suggest that formation of specific water patterns in both grooves is the factor responsible for stabilization of A-tracts with a narrowed minor groove, leading in turn to their strong intrinsic bending in DNA

Structure and Binding Energy of Double-Stranded A‑DNA Mini-helices: Quantum-Chemical Study

A-DNA is thought to play a significant biological role in gene expression due to its specific conformation and binding features. In this study, double-stranded mini-helices (dA:dT)₃ and (dG:dC)₃ in A-like DNA conformation were investigated. M06-2X/6-31G­(d,p) method has been utilized to identify the optimal geometries and predict physicochemical parameters of these systems. The results show the ability of the corresponding mini-helices to preserve their A-like conformation under the influences of solvent, charge, and Na⁺ counterions. Presented structural and energetic data offer evidence that two steps of GG/CC or AA/TT are already enough to turn the DNA helix to generate different forms by favoring specific values of roll and slide at a local level. Our calculations support the experimentally known fact that AA/TT steps prefer the B-form over the A-ones, whereas GG/CC steps may be found in either the B- or A-form. The stability of mini-helices at the level of total energy analysis, Δ<i>E</i>_total^(A–B), is discussed