Ion-Dependent Conformational Plasticity of Telomeric G-Hairpins and G-Quadruplexes.

Telomeric DNA is guanine-rich and can adopt structures such as G-quadruplexes (GQs) and G-hairpins. Telomeric GQs influence genome stability and telomerase activity, making understanding of enzyme-GQ interactions and dynamics important for potential drug design. GQs have a characteristic tetrad core, which is connected by loop regions.

Cation competition and recruitment around the c-kit1 G-quadruplex using polarizable simulations.

Nucleic acid-ion interactions are fundamentally important to the physical, energetic, and conformational properties of DNA and RNA. These interactions help fold and stabilize highly ordered secondary and tertiary structures, such as G-quadruplexes (GQs), which are functionally relevant in telomeres, replication initiation sites, and promoter sequences. The c-kit proto-oncogene encodes for a receptor tyrosine kinase and is linked to gastrointestinal stromal tumors, mast cell disease, and leukemia.

Ion Binding Properties and Dynamics of the 2 G-Quadruplex Using a Polarizable Force Field.

G-quadruplexes (GQs) are topologically diverse, highly thermostable noncanonical nucleic acid structures that form in guanine-rich sequences in DNA and RNA. GQs are implicated in transcriptional and translational regulation and genome maintenance, and deleterious alterations to their structures contribute to diseases such as cancer. The expression of the B-cell lymphoma 2 (Bcl-2) antiapoptotic protein, for example, is under transcriptional control of a GQ in the promoter of the 2 gene.

Recent developments in empirical atomistic force fields for nucleic acids and applications to studies of folding and dynamics.

Nucleic acids play critical roles in carrying genetic information, participating in catalysis, and preserving chromosomal structure. Despite over a century of study, efforts to understand the dynamics and structure-function relationships of DNA and RNA at the atomic level are still ongoing. Molecular dynamics (MD) simulations augment experiments by providing atomistic resolution and quantitative relationships between structure and conformational energy.

Polarizable Molecular Dynamics Simulations of Two Oncogene Promoter G-Quadruplexes: Effect of Primary and Secondary Structure on Loop and Ion Sampling.

G-quadruplexes (GQs) are highly ordered nucleic acid structures that play fundamental roles in regulating gene expression and maintaining genomic stability. GQs are topologically diverse and enriched in promoter sequences of growth regulatory genes and proto-oncogenes, suggesting that they may serve as attractive targets for drug design at the level of transcription rather than inhibiting the activity of the protein products of these genes. The promoter contains three adjacent GQ-forming sequences that have proposed antagonistic effects on gene expression and thus are promising drug targets for diseases such as gastrointestinal stromal tumors, mast cell disease, and leukemia.