Journal
JOURNAL OF PHYSICAL CHEMISTRY B
Volume 123, Issue 1, Pages 148-159Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jpcb.8b11026
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Funding
- Virginia Tech Office of the Provost, College of Agriculture and Life Sciences
- USDA-NIFA [VA-160092]
- Virginia Tech Office of the Provost, Department of Biochemistry
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G-quadruplexes (GQs) are guanine-rich, non-canonical nucleic acid structures that play fundamental roles in genomic stability and the regulation of gene expression. GQs are enriched in promoter sequences of growth regulatory genes and proto-oncogenes such as c-kit, which is linked to gastrointestinal stromal tumors, mast cell disease, and leukemia. While GQs have become a popular subject for experimental and computational research, the forces governing GQ dynamics are not fully understood. To gain insights into cation interactions and base-dipole moments of these highly ordered nucleic acid structures, we performed molecular dynamics simulations on the c-kit1 GQ using the CHARMM36 additive and Drude-2017 polarizable force fields. These simulations are the first of their kind to investigate the role of electronic polarization on interactions dictating GQ conformational sampling and cation interactions. Use of a polarizable model revealed differences in base dipole moments between GQs and B-form duplex DNA, force field-dependent ion binding pathways, and allowed for quantification of multibody contributions of water to ion-GQ interactions. These results emphasize the importance of electronic polarization as a contribution to the forces underlying nucleic acid dynamics.
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