Orientation Dependence of Current Blockade in Single Amino Acid Translocation through a Graphene Nanopore ^†

After successful commercialization of DNA sequencing with biological nanopores, the next frontier of the nanopore technology is protein sequencing which is far more daunting a task. Molecules passing through solid-state nanopores produce current blockades that correlate with their volume linearly in the simplest conceivable model. As thinner membranes provide better volume sensitivity, 2D materials such as Graphene, MoS ₂ membranes have been explored. Molecular dynamics studies, mostly of homogeneous polypeptide chains translocating through 2D membranes, have been reported. In this paper, we study the translocation of all the twenty single amino acids through monolayer and bilayer graphene nanopores using all-atom molecular dynamics. These studies were motivated by the fact that single amino-acids being the building blocks of peptide chains, can help us understand pore-molecule interactions during translocations at a more basic level, for instance, avoiding neighbor effects present in a chain. We show here that the correlation between the ionic current blockade and the volume of single amino acids is strongly affected by their orientation at the pore, especially when the molecule is static at pore. We explain this phenomenon by the fact that with increasing vdW volume, the amino acid in a particular orientation, has longer projection along the perpendicular direction of the pore plane. We demonstrate distinctive current and force signals for different amino-acid translocation. We observe that some of the smaller amino acids with low molecular volume produce disproportionately high current blockades in a particular orientation due to their low structural fluctuations during translocation. We investigate how dipole-moment (of the translocating amino-acids) and its alignment with electric field in the pore can be linked with our observations.