Biophysical Society Thematic Meeting| Santa Cruz 2018

Genome Biophysics: Integrating Genomics and Biophysics to Understand Structural and Functional Aspects of Genomes

Poster Abstracts

20-POS Board 20 Sequence Dependence Studies of a 336-bp DNA Circle of Various Topology Through Energy Minimization Calculations Robert T Young 1 ; Pamela J Perez 1 ; Wilma K Olson 1 ; 1 Rutgers University, Chemistry and Chemical Biology, New Brunswick, New Jersey, United States Computational modeling of DNA has aided in understanding how the double helical structure can deform with and without the assistance of proteins. Such deformations allow for genetic and protein regulation as well as higher-order organization within the cell. A contributing factor to such deformability lies in the primary nucleotide sequence of DNA as some nucleotides have different intrinsic characteristics and helical configurations based on the local sequence context. For example, a pyrimidine-purine (YR) dinucleotide step has a greater degree of deformation when compared to pyrimidine-pyrimidine (YY) or purine-purine (RR) steps. Structural deformations, such as domains that are bent or kinked, give rise to supercoiled structures and even disruptions to the hydrogen-bonding network between bases. We explore such sequence dependence through minimum-energy optimization calculations of various DNA conformational rest states and initial conditions, some of which include bent domains within closed circular structures. Calculations were performed on a 336-base pair sequence found in literature on supercoiled diversity among topological variations, with the minimization rest state values based on dimer-specific roll and twist parameters. Initial conditions that were optimized were either of a smooth planar circle, structures generated from molecular dynamic simulations, or figure-8- like circles constructed from protein-mediated DNA loops. Initial optimization calculations were conducted without constraining the initial conditions, the presence of splayed base pairs found in the molecular dynamics-based structures required further optimization calculations where bent and under/over wound domains were constrained in sequence lengths of integral helical turns. These studies provide a step forward in understanding the effect of sequence on naturally- occurring circular DNA structures of various base pair composition and topology as well as the distinction between physical and biological optimal configurations.

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