Conformational Dynamics of the Human Propeller Telomeric DNA Quadruplex on a Microsecond Time Scale

Barira Islam, Miriam Sgobba, Charles Laughton, Modesto Orozco, Jiri Sponer, Stephen Neidle, Shozeb Haider, Shozeb Haider

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)


The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propeller-type topology. NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal-packing interactions that are effectively equivalent to molecular crowding. This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state. While G-quartet stems have been well characterised, the interactions of the TTA loop with the G-quartets are much less defined. To better understand the conformational variability and structural dynamics of the propeller-type topology, we performed molecular dynamics simulations in explicit solvent up to 1.5 µs. The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G-quartets including formation of an A:A base pair, triad, pentad and hexad. The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar-phosphate backbone in formation of unusual architecture within the topology. Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology.
Original languageEnglish
Pages (from-to)2723
Number of pages2735
JournalNucleic Acids Research
Issue number4
Publication statusPublished - 01 Feb 2013

ASJC Scopus subject areas

  • Genetics

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