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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Protein Cell ›› 2015, Vol. 6 ›› Issue (6) : 423-433. DOI: 10.1007/s13238-015-0155-3
RESEARCH ARTICLE

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

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Abstract

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.

Keywords

G-quadruplex / potassium ion / molecular dynamics / principal component analysis / MM-PBSA

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Zhiguo Wang, Ruping Chen, Ling Hou, Jianfeng Li, Jun-Ping Liu. Molecular dynamics and principal components of potassium binding with human telomeric intra-molecular G-quadruplex. Protein Cell, 2015, 6(6): 423‒433 https://doi.org/10.1007/s13238-015-0155-3

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2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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