ISLAM, Barira, Petr STADLBAUER, Miroslav KREPL, Jaroslav KOČA, Stephen NEIDLE, Shozeb HAIDER and Jiří ŠPONER. Extended molecular dynamics of a c-kit promoter quadruplex. Nucleic Acids Research. Oxford: Oxford University Press, vol. 43, No 18, p. 8673-8693. ISSN 0305-1048. doi:10.1093/nar/gkv785. 2015.
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Basic information
Original name Extended molecular dynamics of a c-kit promoter quadruplex
Authors ISLAM, Barira (356 India, belonging to the institution), Petr STADLBAUER (203 Czech Republic), Miroslav KREPL (203 Czech Republic), Jaroslav KOČA (203 Czech Republic, belonging to the institution), Stephen NEIDLE (203 Czech Republic), Shozeb HAIDER (203 Czech Republic) and Jiří ŠPONER (203 Czech Republic, guarantor, belonging to the institution).
Edition Nucleic Acids Research, Oxford, Oxford University Press, 2015, 0305-1048.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10600 1.6 Biological sciences
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 9.202
RIV identification code RIV/00216224:14740/15:00086620
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.1093/nar/gkv785
UT WoS 000366406500014
Keywords in English TELOMERIC G-QUADRUPLEX; INTRAMOLECULAR DNA QUADRUPLEXES; GASTROINTESTINAL STROMAL TUMOR; PARALLEL G-QUADRUPLEXES; PARTICLE MESH EWALD; AMBER FORCE-FIELD; G-TRACT LENGTH; RNA LOOP-E; NUCLEIC-ACIDS; ION-BINDING
Tags OA, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Eva Špillingová, učo 110713. Changed: 5/4/2016 15:51.
Abstract
The 22-mer c-kit promoter sequence folds into a parallel-stranded quadruplex with a unique structure, which has been elucidated by crystallographic and NMR methods and shows a high degree of structural conservation. We have carried out a series of extended (up to 10 mu s long, similar to 50 mu s in total) molecular dynamics simulations to explore conformational stability and loop dynamics of this quadruplex. Unfolding no-salt simulations are consistent with a multi-pathway model of quadruplex folding and identify the single-nucleotide propeller loops as the most fragile part of the quadruplex. Thus, formation of propeller loops represents a peculiar atomistic aspect of quadruplex folding. Unbiased simulations reveal mu s-scale transitions in the loops, which emphasizes the need for extended simulations in studies of quadruplex loops. We identify ion binding in the loops which may contribute to quadruplex stability. The long lateral-propeller loop is internally very stable but extensively fluctuates as a rigid entity. It creates a size-adaptable cleft between the loop and the stem, which can facilitate ligand binding. The stability gain by forming the internal network of GA base pairs and stacks of this loop may be dictating which of the many possible quadruplex topologies is observed in the ground state by this promoter quadruplex.
Links
ED1.1.00/02.0068, research and development projectName: CEITEC - central european institute of technology
EE2.3.30.0037, research and development projectName: Zaměstnáním nejlepších mladých vědců k rozvoji mezinárodní spolupráce
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