Doctor of Philosophy (PhD)


Mechanical Engineering

Document Type



There is potential for flight time based DNA sequencing involving disassembly into individual nucleotides which would pass through a nanochannel with 2 or more detectors. Molecular dynamics simulation of electrophoretic motion of single DNA nucleotides through 3 nm wide hydrophobic slits was performed. Electric field strength (E) varied from 0.0 to 0.6 V/nm. Slit walls were smooth or had a roughness similar to nucleotide size. Multiple nucleotide-wall adsorptions occurred. The electric field did not influence the nucleotide adsorption and desorption mechanism for E ¡Ü 0.1 V/nm, but influenced nucleotide orientation relative to the field direction. The nucleotide-wall interactions differed due to nucleotide hydrophobicities and wall roughness, and determined duration and frequency of nucleotide adsorptions and their velocities while adsorbed. Transient association of nucleotides with 1 to 3 sodium ions occurred but the mean association numbers (AN) were weak functions of nucleotide type. ANs for pyrimidine nucleotides were slightly lower than for purine nucleotides. Nucleotide-wall interactions contributed more to separation of nucleotide flight time distributions than ion association. A PMMA slab was built and a CHARMM force field file modified from the force field for a PMMA trimer was verified and then utilized to study the transport of dNMPs through PMMA nanoslits. The simulation studies show that, while moving along the PMMA nanoslit the mononucleotides are adsorbed and desorbed from the walls multiple times. Due to their strong interaction with the PMMA walls the mononucleotides can be trapped in adsorbed state for hundreds of nanoseconds. When dNMPs are in the desorbed state, their traveling velocity along the axis of the nanochannel is mainly affected by the association between Na+ and the phosphate group. The Brownian MD simulation studies show that, the main characteristics of the mononucleotides through a nanochannel can be obtained by performing simulations of the dNMPs-PMMA wall system using a coarse-grained representation of the system. The accuracy of this method depends on the accuracy of the potential of mean force used to describe the interaction between dNMP and the PMMA wall.



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Committee Chair

Moldovan, Dorel