Investigating the structure and physical properties of nucleic acids in nanoscale confinement

While significant advancements have been achieved in deciphering genetic sequences, our understanding of the structures of extensive nucleic acids, such as biological system genomes, remains comparatively limited. Viruses, being the simplest of organisms, offer a distinctive vantage point for physicists drawn to a reductionist approach, enabling them to uncover fundamental principles underlying complex biological systems. However, despite the resolution of protein capsid structures across multiple systems, insights into their genomic structures remain considerably less developed. Molecular simulations are becoming essential tools, bolstered by powerful supercomputers, enabling heightened accuracy and predictiveness, and instrumental insights. This doctoral thesis encompasses the overarching theme of “modeling of nucleic acids,” interlinking diverse projects across virology and nanotechnology. The initial segment focuses on unraveling the structural and dynamic intricacies of packaged virions, detailed over three chapters dedicated to the resolved viruses, bacteriophage HK97, MS2 and probing their electrophoretic properties with atomistic simulations. The subsequent segment encompasses four chapters, delving into distinct nanotechnology applications arising from separate projects that were done in collaboration with multiple experimental groups. First, I discuss our simulations characterizing Poly(ADP-ribose), a biologically important post translational modification that acts as a flexible binding scaffold in numerous cellular signaling pathways. This project was done in collaboration with the Leung lab at John Hopkins University and the Pollack lab at Cornell University. The next project, in collaboration with the Kornyshev lab at Imperial College London, revisits the effect of water structure on hydration forces. This work examines a phenomenological nonlocal model developed by the Kornyshev lab, in combination with our atomistic molecular dynamics simulations, to reveal the nature of the electric field around a single DNA molecule. The last two chapters describe two collaborative projects that are poised to disentangle the multitude of competing phenomena pertaining to diffusion of biomolecules on 2D surfaces. First, I describe our illustrative simulations that unveil the mechanistic intricacies of the innovative ‘graphene energy transfer’ technology, developed by the Tinnefeld lab at LMU, Germany. Finally, I conclude with our simulations that characterize the diffusion of ssDNA fragments on hBN surfaces, and the effect of microscopic surface defects. This work was done in collaboration with the Steeneken and Joo labs at TU Delft, Netherlands. Throughout the culmination of this doctoral endeavor, the journey was replete with unforeseen challenges met with improvisations. In conclusion, I offer a pedagogical exposition of these experiences, aiming to furnish meticulous insights that may preempt similar obstacles in future pursuits.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics & Quant Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Coshic, Kush

Contributors dc:contributor

• Aksimentiev, Aleksei
• Schulten, Zaida Luthey
• Tajkhorshid, Emad
• Chemla, Yann R.

• Viral Genome
• Molecular Dynamics
• Multiscale Modeling
• Multiresolution
• Computational Modeling
• Nanotechnology
• 2d Surface
• Nucleic Acid
• Nanoscale Confinement
• Structure

Statement dc:rights

• © 2023 Kush Coshic

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/122221

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F122221