Supervisor: Lukáš Trantírek

Annotation: DNA guanine quadruplexes (G4) belong to the most important noncanonical nucleic acid structures. They regulate gene expression, are potential pharmacological targets, and are often used as a basis for DNA supramolecular assemblies and nanostructures. G4 molecules have intriguing folding mechanisms, which appear to be unique in the biomolecular world. Understanding of the basic principles of folding of biomolecules is an important scientific question per se.

The aim of the project is to study folding mechanisms of G4s and some other types of noncanonical nucleic acids using state of the art atomistic molecular dynamics (MD) simulations. The computational research will be conducted in one of the world-leading laboratories in the field of nucleic acids simulations, in a close collaboration with experimental laboratories, leading to clear interrelation between theory and experiment. The main techniques will be standard and diverse enhanced-sampling MD simulations; part of the research may be even development of cutting-edge methods (force fields and enhanced sampling protocols) for studies of biomolecular folding.

Perspective student should have done masters in physical chemistry, biochemistry, or related fields and have proven experience with computational chemistry applied to biomolecules. We expect dedication to solve intriguing scientific questions.

Recommended literature:

  • Šponer, J.; Bussi, G.; Krepl, M.; Banáš, P.; Bottaro, S.; Cunha, R. A.; Gil-Ley, A.; Pinamonti, G.; Poblete, S.; Jurečka, P., et al., RNA Structural Dynamics as Captured by Molecular Simulations: A Comprehensive Overview. Chemical Reviews, 2018, 118, 4177–4338, DOI: 10.1021/acs.chemrev.7b00427
  • Šponer, J.; Bussi, G.; Stadlbauer, P.; Kührová, P.; Banáš, P.; Islam, B.; Haider, S.; Neidle, S.; Otyepka, M., Folding of Guanine Quadruplex Molecules–funnel-like Mechanism or Kinetic Partitioning? An Overview from MD Simulation Studies. Biochimica et Biophysica Acta (BBA) – General Subjects, 2017, 1861, 1246–1263, DOI: 10.1016/j.bbagen.2016.12.008
  • Živković, M. L.; Gajarský, M.; Beková, K.; Stadlbauer, P.; Vicherek, L.; Petrová, M.; Fiala, R.; Rosenberg, I.; Šponer, J.; Plavec, J.; Trantírek, L., Insight into Formation Propensity of Pseudocircular DNA G-hairpins. Nucleic Acids Research, 2021, 49, 2317–2332, DOI: 10.1093/nar/gkab029
  • Stadlbauer, P.; Kührová, P.; Vicherek, L.; Banáš, P.; Otyepka, M.; Trantírek, L.; Šponer, J., Parallel G-triplexes and G-hairpins as Potential Transitory Ensembles in the Folding of Parallel-stranded DNA G-Quadruplexes. Nucleic Acids Research, 2019, 47, 7276–7293, DOI: 10.1093/nar/gkz610

More information on CEITEC PhD School website: https://ls-phd.ceitec.cz/ and Research Group website: https://www.ceitec.eu/non-coding-genome/rg109

In case you are interested. ​Please, submit your CV and motivation letter via Registration Form.

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