Topological organization is an essential feature of bio-macromolecules affecting their properties, for instance unique protein folding enables proper function of molecular machines, or higher-order organization of DNA enables storage and active usage of genetic information in dense environment inside cell core. Backbone of DNA molecule composed of D-deoxyribose (or D-ribose in RNA) introduces asymmetry leading in complex structure with chiral features at all levels of structural organization from right-handed α-helix in secondary structure, through nucleosome units wrapped around histones, knots and catenanes, up to plectonemes and supercoils. In general, we know that chirality plays an important role in biological systems, yet there are still mysteries to uncover. Abundance of certain form of chiral knots was experimentally discovered [1] by 2D-gel electrophoresis, where the structure of knot was altered by supercoiling. The interplay between chirality of knot and chirality of supercoiling induces symmetry breaking and enhances differences between enantiomers. We would like to apply the same principle with suitable confinement, which could be used for separation of chiral entanglements without altering their structure. In our study, we put various types of knots (chiral, achiral, torus, twist, etc.) in three types of confinement (cylinder, torus, helix) and we investigate structural and dynamical properties of the knots. For our study, we use molecular dynamics simulation, which enables detailed investigation of one molecule system with unified size and pre-defined topology. Progress in chemical synthesis enables tailoring molecules with given geometrical properties. Therefore, experimental application of our system could be conducted for instance by self-assembled chiral nanotubes [2].
Support from the Grant Agency of Ministry of Education VEGA-2/0102/20, Slovak-Austrian SRDA-SK-AT-20-0011, SRDA-15-0323, and COST 17 139 EUTOPIA is acknowledged.
Nice piece of work, thank you
Nice piece of work, thank you. Could you explain what the abbreviations „(Visualization –) VMD, POV-RAY” stand for? Is it a freeware?
And ... is it possible to combine theoretical and experimental studies for the chiral discrimination of “your” structures?
iwa
Thank you very much for your
Thank you very much for your comment and questions.
VMD is Visual Molecular Dynamics (http://www.ks.uiuc.edu/Research/vmd/), it is used for visualization and animation of large biomolecular systems in 3D graphics. In our work, it was used for snapshots of the simulation and quick check of the structure. You can see it in the presentation at slide num.8 at describing the simulation setup or slide n.9 as insets of knotted structures in graphs.
POV-RAY is The Persistence of Vision Raytraycer (http://www.povray.org/) used for high quality graphical design. All the simulation snapshots with knotted structure inside helical structure (slides 10,11,12), as well as DNA model at the bottom of Methodology section (slide 6) were obtained via POV-RAY
Both are free of charge and run on several types of OS.
Experimentally, it was possible to separate chiral knots through 2-D gel electrophoresis, where their structure was altered by negative supercoiling [1]. In our work, we are trying to set up a theoretical basis for chiral separation method, which would separate the knots without altering their structure through geometrical confinement. It could be experimentally tested for example by driving DNA knots through an array of chiral nanotubes by electrical current. Such nanotubes could be self-assembled pyridine-pyridazine oligomers, for instance [2], or any other nanotube with chiral components.
1. Antonio Valdés, Belén Martínez-García, Joana Segura, Sílvia Dyson, Ofelia Díaz-Ingelmo, Joaquim Roca, Quantitative disclosure of DNA knot chirality by high-resolution 2D-gel electrophoresis, Nucleic Acids Research, Volume 47, Issue 5, 18 March 2019, Page e29, https://doi.org/10.1093/nar/gkz015
2. Yan, Tengfei & Yang, Feihu & Qi, Shuaiwei & Fan, Xiaotong & Liu, Shengda & Ma, Ningning & Luo, Quan & Dong, Zeyuan & Liu, Junqiu. (2019). Supramolecular nanochannels self-assembled by helical pyridine-pyridazine oligomers. Chemical Communications. 55. 10.1039/C8CC10098E.
Thank you for your time to
Thank you for your time to answer my question - as to the abbreviation, I must have ovelooked it somehow - not quite my cup od tea 😉 but always interesting to me and inspiring. Nice that experiments could be carried out in parallel to the computation. I wish you success with your projects.
iwa
Thank you :)
Thank you :)