Validating, Assessing, and Improving Force Fields for Molecular Dynamics Simulations of Nucleic Acids
Abstract: Molecular dynamics (MD) simulations are a valuable computational tool for understanding experimental data, revealing structural intricacies, and uncovering conformational dynamics of biomolecules. Further, MD simulations can be leveraged for use in computer-aided drug design to identify and develop drug candidates. While many biomolecules, including proteins and helical nucleic acids, can be simulated in agreement to experimental data, there are some classes of structures, including single-stranded RNAs, that are still troublesome. This dissertation will highlight both successful applications of MD simulations for use in computer-aided drug design and the development of this method for improving the modeling of challenging nucleic acid structures. First, MD simulations are employed to uncover atomistic-level interactions between small molecules and helical DNA or G-quadruplex targets. Subsequent work describes benchmarking of available force fields for their abilities to reproduce challenging structures and dynamics, including DNA mini-dumbbells, RNA tetranucleotides, or A-DNA helices. Finally, modifications to the current generation of nucleic acid force fields are examined as a route to improve resulting structures. The work presented will showcase noteworthy applications alongside the current limitations of MD simulations for modeling nucleic acids. They define a potential path forward for developing a more accurate tool for use in applications such as structural biology and computer-aided drug design.
November 27th 2023
HSEB 1730 and Zoom
Join Zoom Meeting https://utah-health.zoom.us/j/96697822750
Meeting ID: 966 9782 2750