Atomistic Molecular Dynamics Simulations of DNA Minicircle Topoisomers: A Practical Guide to Setup, Performance, and Analysis.
While DNA supercoiling is ubiquitous in vivo, the structure of supercoiled DNA is more challenging to study experimentally than simple linear sequences because the DNA must have a closed topology in order to sustain superhelical stress. DNA minicircles, which are closed circular double-stranded DNA sequences typically containing between 60 and 500 base pairs, have proven to be useful biochemical tools for the study of supercoiled DNA mechanics. We present detailed protocols for constructing models of DNA minicircles in silico, for performing atomistic molecular dynamics (MD) simulations of supercoiled minicircle DNA, and for analyzing the results of the calculations. These simulations are computationally challenging due to the large system sizes. However, improvements in parallel computing software and hardware promise access to improve conformational sampling and simulation timescales. Given the concurrent improvements in the resolution of experimental techniques such as atomic force microscopy (AFM) and cryo-electron microscopy, the study of DNA minicircles will provide a more complete understanding of both the structure and the mechanics of supercoiled DNA.
Theoretical and Computational Science Center (TaCS), Science Laboratory Building, Faculty of Science, King Mongkut University of Technology Thonburi, 126 Pracha Uthit Road, Bang Mod, Thung Khru, Bangkok, 10140, Thailand. jamesreddeviltna@gmail.com.
Thana
T
Sutthibutpong
School of Physics and Astronomy, University of Leeds, Leeds, LS2 9JT, UK.
Agnes
A
Noy
School of Physics and Astronomy, University of Leeds, Leeds, LS2 9JT, UK.|Astbury Centre for Structural and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK.
Sarah
S
Harris
D019295:Computational Biology / Q000379:methods*; D020285:Cryoelectron Microscopy; D004278:DNA, Superhelical / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012984:Software
D004278:DNA, Superhelical
Atomistic molecular dynamics; DNA supercoiling