Abstract
In this work hydrogen bonding in a diverse set of 36 unnatural and the three natural Watson Crick base pairs adenine (A)–thymine (T), adenine (A)–uracil (U) and guanine (G)–cytosine (C) was assessed utilizing local vibrational force constants derived from the local mode analysis, originally introduced by Konkoli and Cremer as a unique bond strength measure based on vibrational spectroscopy. The local mode analysis was complemented by the topological analysis of the electronic density and the natural bond orbital analysis. The most interesting findings of our study are that (i) hydrogen bonding in Watson Crick base pairs is not exceptionally strong and (ii) the N–H⋯N is the most favorable hydrogen bond in both unnatural and natural base pairs while O–H⋯N/O bonds are the less favorable in unnatural base pairs and not found at all in natural base pairs. In addition, the important role of non-classical C–H⋯N/O bonds for the stabilization of base pairs was revealed, especially the role of C–H⋯O bonds in Watson Crick base pairs. Hydrogen bonding in Watson Crick base pairs modeled in the DNA via a QM/MM approach showed that the DNA environment increases the strength of the central N–H⋯N bond and the C–H⋯O bonds, and at the same time decreases the strength of the N–H⋯O bond. However, the general trends observed in the gas phase calculations remain unchanged. The new methodology presented and tested in this work provides the bioengineering community with an efficient design tool to assess and predict the type and strength of hydrogen bonding in artificial base pairs.
Highlights
Deoxyribonucleic acid (DNA) is one of the most intriguing biomolecules found in nature; it basically encodes all necessary information for the diverse functions of life [1,2,3]
We investigated in this work intermolecular hydrogen bonding in a diverse set of 36 unnatural and the three natural Watson Crick base pairs adenine (A)–thymine (T), adenine (A)–uracil (U) and guanine (G)–cytosine (C)
The hydrogen bond strength was assessed utilizing local vibrational force constants derived from the local mode analysis, originally introduced by Konkoli and Cremer as a unique bond strength measure based on vibrational spectroscopy
Summary
Deoxyribonucleic acid (DNA) is one of the most intriguing biomolecules found in nature; it basically encodes all necessary information for the diverse functions of life [1,2,3]. In the early 1950s, a race started to determine the structure of this fascinating biomacromolecule [4,5,6,7]. Corey published an article in February of 1953 [8] proposing a triple helix DNA structure with the bases oriented at the outside. Pauling’s and Corey’s model was proven to be incorrect by Watson and Crick a couple of months later [9] they were one of the first scientists who came to the important conclusion that genes are segments of DNA that contain the code for a specific protein determining its function in different cells in the body, which can be considered as a first milestone for gene sequencing and gene cloning [10,11]. Why nature has decided to use just these two base pair combinations remains one of the greatest mysteries [15,16]
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