2D-MES · Two Dimensional Molecular Electronics Spectroscopy for DNA/RNA Mutation Recognition
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-07-01 → 2023-06-30
- EU contribution
- €172,932
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Two Dimensional Molecular Electronics Spectroscopy for DNA/RNA Mutation Recognition
In this project, a combination of quantum mechanical and classical methods has been used with electronic transport techniques to evaluate the sensing capabilities of two-dimensional (2D) based biosensors to identify DNA and RNA nucleobases (NB) and mutations. Developing fast, reliable, and cost effective, yet practical DNA/RNA sequencing methods and devices is a must. The ability to sequence (i.e. determine the precise order of NBs within a DNA molecule) an organism’s genome and detect probable mutations has radically changed many aspects of molecular biology and genetics in both the academic and private sectors, with applications in molecular medicine, bio-archaeology, anthropology, evolution, forensics, agriculture and livestock breeding. One significant benefit is investigating various diseases and genetic illnesses caused by mutations, for which inexpensive and accurate methods for DNA sequencing are essential. Several computational methodologies, such as simulations of electronic transport in nanopore, or nanochannel-based biosensors, have been fruitfully used to address important phenomena related to DNA sequencing and detection at the molecular level. However, they generally either rely on quantum mechanics (QM) approaches, and are hence limited to small systems, or they employ molecular mechanics (MM) methods, which lack accuracy in certain sensitive cases. The market for next-generation approaches is expected to grow by up to $14 billion by 2024. Some of these approaches exploit the extraordinary properties of (2D) materials to recognize mutated DNA (or mRNA, messenger RNA that conveys the genetic information from DNA) bases at the single molecule level.) In this project, the new concept of Fano resonance-driven 2D molecular electronic spectroscopies (2D-MES), has been employed to enable the recognition of single NBs attached to a 2D material based nanoribbon (2DMNR), and expand it to study, not only isolated NBs, but a more realistic system which includes a complete DNA/RNA sequence in a solvent. In the 2D-MES method, the electrical conductance is calculated against both bias and gate voltages. Sharp dips and/or peaks in the electronic transmission due to the Fano resonance with such MOs represent the molecular fingerprints, which are different for each molecule. Mutation alters the MOs energy levels and their coupling strengths. Consequently, the 2D-MES method is able to distinguish mutated NBs from normal ones with high spatial resolution in a fast and non-expensive way.
Data: CORDIS, © European Union
Project objective
In this project, Dr. Reza Rezapour will address, by a combination of quantum mechanical and classical simulations combined with electronic transport techniques, the sensing capabilities of graphene-based biosensors to identify DNA and RNA mutations in PNA-functionalized graphene nanoribbons.In the search for fast, inexpensive and accurate tools for DNA sequencing and mutation recognition, computational techniques are being fruitfully used to address detection at the molecular level. We will extended the 2D-MES method previously developed by Dr. Rezapour to the identification, not only of single normal and mutated nucleobases on graphene, but of base mutations in DNA or RNA fragments attached to a graphene nanoribbon (GNR) in an aqueous environment. To this aim, after the quantum mechanical (QM) calculation of the transport characteristics of a nucleobases-GNR system in vacuum, we will study: (1) large DNA/RNA fragments in a solvent by molecular mechanics (MM) classical methods (to study mutation stability in a given sequence) and (2) the most stable mutations on a GNR by novel hybrid QM/MM simulations combining the accuracy of QM with the speed of MM.Besides providing new insight on fundamental aspects of physical processes at the interface between solids, liquids and biomolecules, the project will train Dr. Rezapour in advanced new techniques, complementary to his current expertise; and it will provide the community with a new and efficient QM/MM-electronic transport tool by the implementation of transport routines into the existent QM/MM package. The obtained QM/MM transport molecular fingerprints of the mutated DNA/RNA on the GNR will serve as a proof-of-concept for the design of a graphene-based bionsensor fast, inexpensive, and with high spatial resolution.
Original text from CORDIS.
Participants
- UNIVERSIDAD DE GRANADA · GranadaCoordinatorSpain
Links
Data: CORDIS, © European Union