Skinny and fat DNA

Abstract

DNA is where all the genetic information necessary for the functioning, development, growth and reproduction of living things is stored. It is responsible for transmitting the instructions required to create other components of cells, such as proteins. It is composed of two long polymers placed antiparallelly that intertwine to form a double helix. These two chains are composed of nucleotides. The nitrogenous bases of nucleotides can be: adenine (A), cytosine (C), guanine (G), and thymine (T). They always are linked, by hydrogen bonds, adenines with thymines and cytosines with guanines, i.e., a purine with a pyrimidine. These base pairs alternate with each other at an angle of 35 º and are stabilized by π-π stacking interactions. Recent studies start to investigate with artificial bases in order to introduce them into DNA so that it can store more information and build different proteins. This would allow, among other things, a benefit in medicine. One of these recent studies has created two groups of artificial bases: skinny and fat. The skinny are pairs of pyrimidines and the fat pairs of purines; therefore, the size complementarity of natural nitrogenous bases (AT and GC) is not followed. In this project, a computational study of the systems formed for the different artificial pairs and natural pairs is made in order to check if the artificial bases are stable enough to introduce them into the DNA. The parameters investigated are the optimal twist angle, the π-π stacking interactions in the gas and water phases and the effect caused by different substituents on this interaction. The results obtained show that, despite having a wide range of angles, they differ very little between optimal angle energy and the energy at 35 º, the original DNA, which would allow the artificial bases to be they adapted to it correctly. In addition, π-π stacking interactions are similar or superior to those produced by natural bases, implying greater system stability. The base pairs CV and BP have been selected to check the effect of the substituents, because they have been the ones that have obtained a more favourable interaction energy. In the case of the CV, there has been an improvement with EWG substitutes, but EDG do not affect it. In contrast, in the case of BP, there has been a lot of variability, although in general, better results have also been obtained with an EWG substituent. In this way, it can be concluded that the results obtained show that the artificial bases are stable and open up a world of possibilities