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DIPC–PAMS theory workshop

Towards reality in modelling of molecular electronics

June 13-17, 2016 ▪ Donostia-San Sebastián, Spain

Invited talk

Simulating DNA sequencing using a combination of non-equilibrium Green's functions and QM/MM methods

A. R. Rocha

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 [1]. Unfortunately, currently available techniques are unlikely to reach the low cost per genome required for this procedure to become widely available in preventive healthcare [2].

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 [5].

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 [6]. 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.

[1] F. S. Collins, E. D. Green, A. E. Guttmacher, and M. S. Guyer, Nature 422, 835 (2003).

[2] B. S. Shastry, The Pharmacogenomics Journal 6, 16 (2006).

[3] 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).

[4] C. Dekker, Nature Nanotechnology 2, 209 (2007).

[5] M. Zwolak and M. Di Ventra, Nano Letters 5, 421 (2005).

[6] 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).