Simulating DNA sequencing using a combination of non-equilibrium Green's functions and QM/MM methods
Instituto de Física Teórica, Universidade Estadual Paulista (UNESP), São Paulo, SP, Brazil
The quest for rapid whole-genome sequencing using new inexpensive techniques is at the forefront of scientific research as we aim to reliably determine genetic predispositions to diseases and gain a deep understanding of our genetic code . Unfortunately, currently available techniques are unlikely to reach the low cost per genome required for this procedure to become widely available in preventive healthcare .
Third-generation devices, in particular, sequencing with nanopores [3,4], is widely regarded as the most promising approach to enable inexpensive whole-genome sequencing and provide orders of magnitude longer base read-lengths. The fabrication of solid-state nanopores along with their envisioned application for rapid whole-genome sequencing is becoming increasingly sophisticated. However, many extremely challenging questions remain unanswered, especially how to achieve single-base resolution during polynucleotide translocation through the nanopore. One proposal is to use tunneling current across the membrane containing the nanopore and use the different electronic transport signals as a signature of the electronic structure of the different nucleotides .
From the theoretical point of view this is a challenging, yet exciting task. On the one hand one must simulate the dynamics of DNA as it passes through a nanopore. The molecule is surrounded by a physiological solution. At the same electrons must be explicitly tread as one wishes to calculate the current passing through the device. In this talk I will discuss recent progress in our group towards completely and realistically simulating a nanopore-based sequencing device . In order to do this, I'll demonstrate how we combine quantum and classical methodologies in order to address the electronic conductance and the possibility of using graphene-based devices for single-shot DNA sequencing.
 F. S. Collins, E. D. Green, A. E. Guttmacher, and M. S. Guyer, Nature 422, 835 (2003).
 B. S. Shastry, The Pharmacogenomics Journal 6, 16 (2006).
 J. J. Kasianowicz, E. Brandin, D. Branton, and D. W. Deamer, Proceedings of the National Academy of Sciences of the United States of America 93, 13770 (1996).
 C. Dekker, Nature Nanotechnology 2, 209 (2007).
 M. Zwolak and M. Di Ventra, Nano Letters 5, 421 (2005).
 G. T. Feliciano, C. Sanz-Navarro, M. D. Coutinho-Neto, P. Ordejón, R. H. Scheicher and A. R. Rocha, Nature Communications, Phys. Rev. App. (2015).