Conformational dynamics of the human propeller telomeric DNA quadruplex on a microsecond time scale

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

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propellertype 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. Although G-quartet stems have been well characterized, 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 ks. 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)2723-2735
Number of pages13
JournalNucleic Acids Research
Issue number4
Early online date3 Jan 2013
Publication statusPublished - 1 Feb 2013
Externally publishedYes


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