Hydrogen Bonding in Natural and Unnatural Base Pairs—A Local Vibrational Mode Study

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.

CO bonding in hexa‐ and pentacoordinate carboxy‐neuroglobin: A quantum mechanics/molecular mechanics and local vibrational mode study

“…The smaller strength of the classical O···H–N hydrogen bonds is due to a specific orientation of the distal histidine relative to CO coordinated to the heme group, in which the N–H group of the histidine side chain is oriented closer to the CO carbon atom rather than the CO oxygen atom, making C···H–N dispersion interactions stronger than O···H–N hydrogen bonding. As pointed out in our previous study on hydrogen bonding in bases pairs, 177 non‐classical hydrogen bonding plays a non‐negligible role in biochemical systems, and depending on the topology of the system they can be stronger the classical hydrogen bonds.…”

“…In their landmark paper, Zou and Cremer 138 proved that the local stretching force constant k a n (AB) reflects the intrinsic strength of the bond/interaction between two atoms A and B being described by an internal coordinate q n . In essence, LMA has advanced as a powerful analytical tool, extensively applied to a broad range of chemical systems from simple molecular systems to systems in solution 139,140 and proteins 102,141 accounting for both covalent bonds 79,88,131,138,142–152 and non‐covalent interactions 89,150,153–166 including hydrogen bonds 167–177 . Recently, a whole new scope of chemical systems were unlocked with the extension of LVM theory to periodic systems 178 …”

“…In essence, LMA has advanced as a powerful analytical tool, extensively applied to a broad range of chemical systems from simple molecular systems to systems in solution 139,140 and proteins 102,141 accounting for both covalent bonds 79,88,131,138,[142][143][144][145][146][147][148][149][150][151][152] and noncovalent interactions 89,150,[153][154][155][156][157][158][159][160][161][162][163][164][165][166] including hydrogen bonds. [167][168][169][170][171][172][173][174][175][176][177] Recently, a whole new scope of chemical systems were unlocked with the extension of LVM theory to periodic systems. 178 For the comparison of larger sets of k a va...…”

Papaya Leaf Extracts as Potential Dengue Treatment: An In-Silico Study

“…[ 99 , 100 , 101 ] tetrel bonds, ref. [ 102 ], and hydrogen bonds [ 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 ]. It is convenient to base the comparison of the bond strength for the set of molecules on a chemically more-prevalent bond strength order (BSO n) rather than on a comparison of local force constant values.…”

Capturing Individual Hydrogen Bond Strengths in Ices via Periodic Local Vibrational Mode Theory: Beyond the Lattice Energy Picture

“…The reader is encouraged to refer to a comprehensive review by Kraka et al on the origin and applications of LVM theory. In essence, LVM analysis has advanced as a powerful analytical tool, extensively applied to a broad range of chemical systems from simple molecular systems to systems in solution , to proteins , accounting for both covalent bonds − and noncovalent interactions ,− including H-bonds. − Recently, a whole new scope of chemical systems were unlocked with the extension of LVM theory to periodic systems of one- through three-dimensions, which has enabled us to probe the nature of crystal bonding. A LVM in a periodic system is defined as a vibration driven by a specific internal coordinate in all primitive cells while relaxing all other parts of the periodic system.…”