Hairpins participating in folding of human telomeric sequence quadruplexes studied by standard and T-REMD simulations

0456040 - BFÚ 2016 RIV GB eng J - Journal Article
Stadlbauer, Petr - Kuehrova, P. - Banáš, P. - Koča, J. - Bussi, G. - Trantírek, L. - Otyepka, M. - Šponer, Jiří
Hairpins participating in folding of human telomeric sequence quadruplexes studied by standard and T-REMD simulations.
Nucleic Acids Research. Roč. 43, č. 20 (2015), s. 9626-9644. ISSN 0305-1048. E-ISSN 1362-4962
R&D Projects: GA ČR(CZ) GAP208/11/1822
Institutional support: RVO:68081707
Keywords : MOLECULAR-DYNAMICS SIMULATIONS * INTRAMOLECULAR DNA QUADRUPLEXES * PARTICLE MESH EWALD
OECD category: Biochemistry and molecular biology
Impact factor: 9.202, year: 2015
Method of publishing: Open access
https://academic.oup.com/nar/article/43/20/9626/1403100

DNA G-hairpins are potential key structures participating in folding of human telomeric guanine quadruplexes (GQ). We examined their properties by standard MD simulations starting from the folded state and long T-REMD starting from the unfolded state, accumulating similar to 130 mu s of atomistic simulations. Antiparallel G-hairpins should spontaneously form in all stages of the folding to support lateral and diagonal loops, with sub-mu s scale rearrangements between them. We found no clear predisposition for direct folding into specific GQ topologies with specific syn/anti patterns. Our key prediction stemming from the T-REMD is that an ideal unfolded ensemble of the full GQ sequence populates all 4096 syn/anti combinations of its four G-stretches. The simulations can propose idealized folding pathways but we explain that such few-state pathways may be misleading.
Permanent Link: http://hdl.handle.net/11104/0256640