Molecular dynamics and principal components of potassium binding with human telomeric intra-molecular G-quadruplex

Zhiguo Wang, Ruping Chen, Ling Hou, Jianfeng Li, Jun-Ping Liu

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10 Citations (Scopus)


Telomere assumes intra-molecular G-quadruplex that is a significant drug target for inhibiting telomerase maintenance of telomeres in cancer. Metal cations have been recognized as playing important roles in stabilizing G-quadruplex, but their binding processes to human telomeric G-quadruplex remain uncharacterized. To investigate the detailed binding procedures, molecular dynamics simulations were conducted on the hybrid [3 + 1] form-one human telomeric intra-molecular G-quadruplex. We show here that the binding of a potassium ion to a G-tetrad core is mediated by two alternative pathways. Principal component analysis illustrated the dominant concerted motions of G-quadruplex occurred at the loop domains. MM-PBSA calculations revealed that binding was energetically favorable and driven by the electrostatic interactions. The lower binding site was found more constructive favorable for binding. Our data provide useful information on a potassium-mediated stable structure of human telomeric intra-molecular G-quadruplex, implicating in ion disorder associated conformational changes and targeted drug design.

Original languageEnglish
Pages (from-to)423-433
Number of pages11
JournalProtein & Cell
Issue number6
Publication statusPublished - 29 Jun 2015


  • G-quadruplex
  • molecular dynamics
  • potassium ion
  • principal component analysis

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