Thesis title: A new bottom-up paradigm for protein sequencing: ab-initio models of mesoscopic tunneling transport in nanogaps of graphene nanoribbons.
The importance of identifying proteins’ sequence and the 3D structure is crucial to understand their function and behavior within living organisms. For instance, the best approach to understand and to diagnose some kind of cancer, cerebrovascular diseases and neurodegenerative diseases is looking at changes in the proteome profile of the cells. Current methods such as Edman degradation and mass spectrometry respectively require long sequencing times and a concentration of the analyte relatively too high for a full coverage of the cell proteome. Then, fast and efficient techniques are required (especially for large protein chains) and solid-state nanopores and nanogaps are emerging as promising tools for single molecule analysis. In this framework, a new sequencer consisting of arrays of nano-gaps between graphene nanoribbons (GNR) is proposed. The atomistic resolution provided by the measuring of the transverse current permits, in principle, to recognize the passage of the amino acid translocating between the two leads. A DFT-based ab initio study, in conjunction with the Non-Equilibrium Green Function (NEGF) method and the Landauer-Büttiker approach, was conducted. Exploiting the 2D structure of the electrodes, it has been evidenced that this ideal device is capable of an atomistic resolution in sensing the peptide bonds (PB) with specific features of the atoms involved. The general idea is to devote the various gaps of the array to sense different parts of the peptide chain, with the central one specifically devoted to get a sort of trigger signal at each peptide bond during the translocation and the lateral ones to the recognition of the specific amino acid using the tunneling current of the side chain. It is important to emphasize that the approach proposed for the detection of the amino acid chain is intimately related to the electronic properties of the device involving the pseudo-π and pseudo-π∗ orbitals of the GNRs electrodes and the PB Molecular Orbitals (MOs). Results have been obtained for simple Gly based template peptides, for which is obtained a characteristic double peak on NH and CO configurations, with a drop of signal for SC configurations. Later on, the same theoretical approach has been employed to study the signal for nanogaps of increasing sub-nanometer widths up to 0.7 nm, that is practically achievable with the available technology. It was observed that the signal shape changes from a double peak to a single structured one and the peak intensity, although being markedly reduced, still remains well within the measurable range of commercially available pico-ammeters. After that, the study has been extended to some model peptides made of neutral polar (Asp, Asn,Ser) and apolar (Ala) amino acids. The current signals collected show a single residue periodicity: main peaks occur when the mid-bond of the backbone NC bond is in the ZGNR basal plane, just in the middle of the gap. It is also demonstrated that the device proposed could, in principle, differentiates heteropeptides involving Gly alternated with monomers of Asp, Asn, Ser and Ala. All of the four different type of mixed peptides evince a double residue periodicity with the maximum corresponding to the larger residue (Ala, Asn, Ser or Asp), independently on the side chain polar state. So, the peculiarities of the backbone signal coming from different peptides enforce the idea that peptide/protein primary structure sequencing by tunneling current across nanogaps in GNRs could be triggered with atomistic resolution by looking at the tunneling signal coming from the peptide backbone.