Structural variation in circular DNA influenced by nucleotide sequence and rotational rigid body parameters

The physical configuration of double-stranded DNA plays a significant role in the protection and expression of genetic material. Studies of biologically relevant DNA configurations show the importance of covalently-closed, circular structures with lengths less than one thousand base pairs. Smaller circular forms must contend with thermodynamic barriers, such as differences between bending and torsional properties of DNA, that may prevent them from reaching an energetically stable, low-energy state. An elastic energy minimization study was conducted using a base-pair step harmonic potential function to observe deformations of a set of DNA minicircles. The topoisomers, of length 150 base pairs, vary in both linking number and the nucleotide coding sequence, comprised of equal numbers of the purine nucleotides adenine and guanine. The initial portion of the study focuses on differences between optimized states found with two homopolymeric models that represent B-form DNA. Additional complexity was introduced by using sequence-specific intrinsic states, incorporating differences in the twist and the roll component of the intrinsic bend at AA, AG, GA, and GG dimer steps. Results show connections between optimized energetic states and the uptake of twist of DNA as well as changes in local bend and twist, producing high-energy, out-of-plane deformations of the global structures of circles comprised of specific repeated tracts of adenine and guanine. The structural distortions occur in A₄G₄ and A₅G₅ sequence motifs in the form of either kinked polygonal optimized states or states of out-of-plane bending. The connection between global distortions and sequence found here may be related to effects sequences seen in naturally occurring DNA circles. Further studies of chains made up of other sequence motifs or incorporating more realistic modeling of DNA, such as the known elastic coupling between bend and twist, are needed to establish firm connections between sequence and global DNA structure.M.S.Includes bibliographical reference