eprintid: 1470026 rev_number: 47 eprint_status: archive userid: 608 dir: disk0/01/47/00/26 datestamp: 2015-10-08 13:22:17 lastmod: 2021-09-20 00:26:57 status_changed: 2015-10-08 13:22:17 type: article metadata_visibility: show creators_name: Islam, B creators_name: Stadlbauer, P creators_name: Krepl, M creators_name: Koca, J creators_name: Neidle, S creators_name: Haider, S creators_name: Sponer, J title: Extended molecular dynamics of a c-kit promoter quadruplex. ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D10 divisions: G09 note: © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 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 μs long, ∼50 μs 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 μs-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. date: 2015-08-05 official_url: http://dx.doi.org/10.1093/nar/gkv785 vfaculties: VFLS oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: JOURNAL ARTICLE verified: verified_manual elements_id: 1043557 doi: 10.1093/nar/gkv785 pii: gkv785 lyricists_name: Neidle, Stephen lyricists_name: Shozeb, Syed lyricists_id: SNEID18 lyricists_id: SMSSH06 actors_name: Shozeb, Syed actors_id: SMSSH06 actors_role: owner full_text_status: public publication: Nucleic Acids Research volume: 43 number: 18 pagerange: 8673-8693 issn: 1362-4962 citation: Islam, B; Stadlbauer, P; Krepl, M; Koca, J; Neidle, S; Haider, S; Sponer, J; (2015) Extended molecular dynamics of a c-kit promoter quadruplex. Nucleic Acids Research , 43 (18) pp. 8673-8693. 10.1093/nar/gkv785 <https://doi.org/10.1093/nar%2Fgkv785>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/3/Nucl.%20Acids%20Res.-2015-Islam-nar_gkv785.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/4/nar-00989-f-2015-File021.zip document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/5/nar-00989-f-2015-File019.zip document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/6/nar-00989-f-2015-File017.zip document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/7/nar-00989-f-2015-File014.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/8/nar-00989-f-2015-File012.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/9/nar-00989-f-2015-File010.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/10/nar-00989-f-2015-File020.zip document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/11/nar-00989-f-2015-File018.zip document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/12/nar-00989-f-2015-File015.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/13/nar-00989-f-2015-File013.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1470026/14/nar-00989-f-2015-File011.pdf