Ab-initio studies on the interaction of nucleobases and amino acids with metal atoms and surfaces
Title: Ab-initio studies on the interaction of nucleobases and amino acids with metal atoms and surfaces
SNIC Project: SNIC 2019/3-632
Project Type: SNIC Medium Compute
Principal Investigator: Suparna Sanyal <suparna.sanyal@icm.uu.se>
Affiliation: Uppsala universitet
Duration: 2019-12-01 – 2020-12-01
Classification: 10304
Homepage: https://www.icm.uu.se/molecular-biology/sanyal-lab/


The motivation of this project is the application of ab-initio theoretical tools to understand the interaction between nucleic acid bases and amino acids with metal atoms and surfaces, e.g., 2D materials and their heterostructures. These studies are highly relevant from different important directions, e.g., fundamental understanding of the adsorption characteristics of biomolecules on functional surfaces, studies of self-assembly of organic molecules on surfaces for miniaturization of present electronic devices, molecular transport for nanobiotechnogical applications etc. by the quantum mechanical calculations of materials specific properties. In a living cell the genetic material is composed of nucleic acids. Most commonly, it is DNA or deoxyribonucleic acid, which stores the genetic information and replicates to form its copies in each cell-cycle. Other than DNA, which is double stranded and carries deoxy-ribose sugar in its backbone, another important variant of nucleic acid component is RNA or ribonucleic acid. RNA, usually single stranded, has ribose sugar and a slightly different set of bases compared to DNA. The bases present on DNA yields gene sequence, which is transcribed to RNA and finally decoded in proteins. The bases common in DNA and RNA are adenine (A), guanine (G) and cytosine (C). In addition, DNA has thymine (T) that is replaced in RNA by uracil (U). Among these bases A and G are double ringed purine and C, T and U are single ring pyrimidine. Although the basic structures of DNA and RNA are primarily decided by their sugar phosphate backbone and base stacking, yet their overall conformation is determined by many other factors in the cellular environment. Indeed, metal ions play a major role in this process about which very little is known so far. Now that the high resolution crystal structures of macromolecular complexes containing DNA and RNA are being solved, the importance of the metal ions in the structure and function of DNA and RNA are more and more realized. However, historically DNA /RNA was considered to be the study systems for pure biologists where as metal ion based studies were confined mostly among physicists and chemists; thereby creating an artificial barrier between these two areas of science. In this project, we want to bridge these two apparently separated fields of science to study the influence of the metal ions on the conformational behavior and function of the nucleic acids. We will in particular, use Density Functional Theory (DFT) calculations to study the interaction of the alkali and transition metals with RNA and DNA bases and further with respective nucleosides and nucleotides. For this purpose, Vienna Ab initio Simulation Package (VASP) code will be used. Besides standard local density approximation (LDA) or generalized gradient approximation (GGA), we will use hybrid functionals, e.g., B3LYP, HSE etc. recently implemented in the new version of VASP. The reaction barriers will be calculated using nudged elastic band method. In parallel, experiments will be conducted to measure the hyperchromicity of DNA and RNA stretches in the presence of alkali and transition metals using UV-absorbance spectroscopy. From the theoretical side, these spectroscopic properties will be calculated by quantum chemistry based codes, e.g., GAUSSIAN and will be compared with experiments. There is another aspect of this project. It has been shown that the chemical and transport properties of metals and 2D novel materials (graphene and graphene oxide, for example) can be altered by adsorption of nucleic acid bases or nucleosides and nucleotides on those. However, it is still unclear how DNA and RNA elements interact with these substrates carrying different charge properties. Also, the understanding of the structures of the substrates need large scale simulations, which will be executed by LAMMPS and GROMACS codes. Detailed understanding of these features needs systematic investigation, which is lacking so far. We will create systems in silico, where individual DNA and RNA bases (A, G, C, T, U) will be adsorbed on different types of 2D surfaces and their heterostructures. The adsorption energies and geometries along with the binding properties will be studied using DFT calculations. Further, the aim is to complement this study with suitable experiments using spectroscopic methods. It is well known that DFT based on standard LDA or GGA can not take into account the so-called van der Waals interaction, that will play an important role in binding properties. We will include this effect also in our calculations by several methods available nowadays.