Investigation of the effects of mutation on the molecular structure and conductance of DNA:RNA hybrids

Identifying and revealing base sequences of the genetic material (DNA and/or RNA) which is the cornerstone of inheritance, allows detection and identification of disease-causing bacteria and viruses as well as cancer cells. This topic is particularly cruical for clinical diagnosis and research as well as food safety, water and environmental protection, plant and animal pathology and bio-security. Nowadays, in biotechnology and nanotechnology fields, many studies are being carried out to determine the genetic material fast and accurately. The idea of detecting and identifiying molecules via electrical conductance measurements is developped with the first reported measurement of conductance through a single molecule in the early 2000s. As a result of several experimental and theoretical studies, a molecular electronic based bionanosensor idea was developed for the detection of genetic material. A technique capable of detecting a single base change (mutation) in genetic sequences, which are in solutions with attomolar concentration, was developed by analyzing the changes in electrical currents in picoamper level. In this thesis, molecular structures and electrical properties of DNA:RNA hybrids, whose conductance were measured experimentally, were investigated. For this, the three dimensional structure of DNA:RNA hybrids were modelled in AMBER 16 software program using molecular dynamics methods. Analysis of the obtained structures are done by clustering algorithms, which are developed during this study. By using Gaussian 09 software program, quantum mechanics (density functional theory) calculations were performed and molecular orbitals and band structures of DNA:RNA hybrids were analyzed. Then, the probability of electron transmission from one electrode to another was calculated for each structure. As a result, it is shown that conductance is directly related to the three-dimensional structure. It was found that the genetic material could be detected and identified via conductance measurements because of this particular feature. The knowledge obtained with this thesis pave the way for designing probe DNAs for the specific target region of RNA molecules. This study is expected to be a pioneer in the design and development of new biosensor technologies that will contribute to human and public health in the future.