1. Designing modified DNA fragments
Supervisor: prof. Radek Marek
Annotation:The novel forms of nucleotide moieties will be incorporated in silico in oligomers with sequences relevant for biosystems. The biocompatibility of artificial building blocks will be evaluated using advanced methods of quantum chemistry that provide also analytical tools for investigation of crucial noncovalent interactions. Available candidates of modified nucleobases and sugars will be studied experimentally by using NMR spectroscopy in solution.
CUYACOT, Ben J.R., Ivo DURNÍK, Cina FOROUTAN-NEJAD and Radek MAREK. Anatomy of Base Pairing in DNA by Interacting Quantum Atoms, Journal of Chemical Information and Modeling, American Chemical Society, 2020, vol. 60, doi:10.1021/acs.jcim.0c00642.
YURENKO, Yevgen, Jan NOVOTNÝ and Radek MAREK. Weak Supramolecular Interactions Governing Parallel and Antiparallel DNA Quadruplexes: Insights from Large-Scale Quantum Mechanics Analysis of Experimentally Derived Models. Chemistry - A European Journal, Wiley, 2017, vol. 23, p. 5573-5584. doi:10.1002/chem.201700236.
DUREC, Matúš, Francesco ZACCARIA, Célia FONSECA GUERRA and Radek MAREK. Modified guanines as constituents of smart ligands for nucleic acid quadruplexes. Chemistry - A European Journal, Weinheim: Wiley-VCH, 2016, vol. 22, p. 10912-10922. doi:10.1002/chem.201601608.
BAZZI, Sophia, Jan NOVOTNÝ, Yevgen YURENKO and Radek MAREK. Designing a New Class of Bases for Nucleic Acid Quadruplexes and Quadruplex-Active Ligands. Chemistry - A European Journal, Weinheim: Wiley-VCH, 2015, vol. 21, p. 9414-9425. doi:10.1002/chem.201500743.
YURENKO, Yevgen, Jan NOVOTNÝ, Vladimír SKLENÁŘ and Radek MAREK. Substituting CF2 for O4' in Components of Nucleic Acids: Towards Systems with Reduced Propensity to Form Abasic Lesions. Chemistry - A European Journal, WEINHEIM: Wiley, 2015, vol. 21, p. 17933-17943. doi:10.1002/chem.201502977.
Keywords: DNA, base pairing, molecular modelling, quantum chemistry
2. Structure of parallel forms of nucleic acids studied by NMR spectroscopy and molecular modelling
Supervisor: prof. Radek Marek
The project is focused on detailed structural characterization of short purine oligonucleotides clipped by proper sequential motifs that induce parallel orientation of DNA strands. For this purpose, NMR experiments combined with MD simulations will be employed. The effect of modifications of selected nucleotides on the structural properties of designed models will be investigated to gain deeper understanding of key noncovalent interactions that contribute to the folding of such systems.
William Copp, Alexey Y. Denisov, Jingwei Xie, Anne M. Noronha, Christopher Liczner, Nozhat Safaee, Christopher J. Wilds, Kalle Gehring; Influence of nucleotide modifications at the C2’ position on the Hoogsteen base-paired parallel-stranded duplex of poly(A) RNA. Nucleic Acids Research, 2017, 45(17),10321–1033.
Keywords: DNA, base pairing, NMR spectroscopy, molecular modelling