Efficient modeling of DNA translocations and ionic currents using coarse-grained molecular dynamics simulation and finite-element modeling

Choudhary, Adnan

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https://hdl.handle.net/2142/115315 Copy

Description

Title

Efficient modeling of DNA translocations and ionic currents using coarse-grained molecular dynamics simulation and finite-element modeling

Author(s)

Choudhary, Adnan

Issue Date

2021-12-20

Director of Research (if dissertation) or Advisor (if thesis)

Aksimentiev, Aleksei

Doctoral Committee Chair(s)

Song, Jun

Committee Member(s)

• Cooper, Stephen L
• Kim, Sangjin

Department of Study

Physics

Discipline

Physics

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Molecular Dynamics
• Computational Biophysics
• DNA

Abstract

Nanopore sensing is a biophysical analysis technique with wide-ranging applications from DNA and protein sequencing to DNA data storage. While the ionic current signals measured by this technique are useful, their complexity makes interpreting them difficult. For this reason, all-atom and coarse-grained molecular dynamics simulations have been used to relate microscopic translocation details to the experimentally measured ionic current signals. However, traditional coarse-grained simulations don’t predict ionic current signals with atomic resolution, and the usefulness of traditional all-atom simulation is lessened by stringent length and time scale limitations. Here, we perform coarse-grained simulations of DNA translocation through large (100 nm to 1 µm) nanofabricated systems. The transport is driven by an electrostatic profile computed beforehand using continuum modeling. We incorporate the effect of DNA on the conductivity of the simulation volume and employ finite element modeling to calculate the ionic current signals produced by the DNA translocation. We illustrate this method by simulating translocation of DNA through a variety of geometries, including solid-state nanopores, a nanolit, and nanocapillaries. We confirm expected DNA conformations during these translocations, and further identify new con-formations that aid in interpreting experimental results. The electric currents computed by our method demonstrate good quantitative agreement with experiment, and also reveal nanoscopic mechanisms for experimentally observed phenomena. The methodology employed here represents a new approach to quickly and cheaply simulate large scale systems that are inaccessible to all-atom molecular dynamics simulations. The sensitivity of the current estimates to fine details of the DNA motion suggests that these tools could be helpful in guiding experiments. In particular, it may be desirable to use the methodology presented here to check if an experimental system is likely to produce interesting results. Or, it may be used to fine tune parameters in simulation before committing to a particular design in experiment. Lastly, the computational efficiency of this approach allows researchers without access to supercomputing resources to make valuable contributions to the field.

Graduation Semester

2022-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2021 Adnan Choudhary

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