Electrokinetic Brownian Dynamics Simulation of DNA Transport through Nanopore
The relevance of Nanopore Translocation
Nanopore technology has revolutionized the field of DNA sequencing and genomic marker detection by enabling high-throughput, chemical-free, low-cost, and highly accurate analysis of DNA molecules. The technique involves capturing a DNA molecules through a tiny pore (nanopore) drilled in a membrane by the use of electric field bias across the pore and measuring the changes in electrical current as the DNA and the markers passes through the pore. The current patterns in time domain can be used to characterize the DNA sequence and other structural information of the markers.
Computation studies of nanopore translocation of DNA are important and relevant for several reasons:
1. Understanding the underlying physics: Computational studies can provide crucial insights into the non-equilibrium physics of electrophoretically
driven translocation, electrostatic interactions between the DNA molecule and the nanopore, the hydrodynamic drag on the molecule, and the
electro-osmotic forces that drive the translocation process.
This understanding can help in the development of more efficient and accurate sequencing technologies.
2. Designing nanopore sensors: Computational studies can aid in the design and optimization of nanopore sensors for specific applications,
such as detecting specific DNA sequences or analyzing DNA modifications (such as methylation markers).
This can help in the development of highly sensitive and specific
DNA sensors for a wide range of applications, including medical diagnostics, biotechnology, and environmental monitoring.
3. Improving sequencing accuracy: Computational studies also help to improve the accuracy of nanopore sequencing by identifying and
characterizing sources and types of noises and errors in the current data. This can help in the development of better signal processing algorithms by improving
the signal-to-noise ratio and error correction methods.
4. Modeling complex biological processes: Complex biological processes often involve DNA translocation through nanopores and nanochannels,
such as DNA packaging in viruses or DNA repair mechanisms. Moreover, In-silico studies can help in the development of new therapies for diseases
prevention and in the design of novel biomaterials.
How does the ions play a role in translocation?
A typical nanopore experiment is performed under 10 mM to 1M ionic concentration of KCl or NaCl solution. In absence of any obstacles (open pore), a noisy but steady current can be measured due the electro-osmotic flow of the ions (co/counter ions) through the pore. However, when a DNA molecule gets into the pore, a drop in the current is observed. This is due to the fact that the DNA molecule acts as a barrier to the ion flow through the pore. The current drop duration (dwell time) is proportional to the length of the DNA molecule and intensity of the drop contains the characterizing features of the molecule.
What if markers are present along the DNA?
The bio-markers come with different size and shapes depending on their biological origin. The presence of markers further attenuate the ionic current flow. The current drop intensity and duration then can be used to identify the type of the marker.
Our Findings: