Dynamics and Conformational Shifts of d(GGGGTTTTGGGG)₄ DNA Quadruplex: A Molecular Dynamics Simulation Study
Keywords:
G-quadruplex, MD simulation, Torsional and Helicoidal parameters, non-canonical DNAAbstract
Abstract: This study investigated the molecular dynamics (MD) simulation and conformational analysis of a DNA quadruplex, whose crystal structure has been previously reported. The initial coordinates for the DNA quadruplex were sourced from the Protein Data Bank (PDB ID: 1d59), containing the sequence d(GGGGTTTTGGGG)4 from Oxytricha trifallax. This telomeric sequence forms a complex composed of two d(G₄T₄G₄) strands, stabilized by cyclic hydrogen bonding between four guanine bases to form G-quartets. Following the generation of the DNA quadruplex model, a molecular dynamics simulation was conducted using OPLS4 force field over a duration of 100 ns at 300 K. Trajectories of the dynamic pathway were examined at intervals of 10 ns. Structural and conformational changes over a time span of 100 ns were analyzed using the X3DNA software, focusing on RMSD and RMSF plots. The resulting data was compared with the known crystal structure of the DNA quadruplex. The molecular dynamics simulation showed that at 300 K the quadruplex retained its B-type DNA conformation (as the original structure parameters) but with slight structural variations suggesting potential therapeutic relevance. Additionally, Principal Component Analysis (PCA) applied to the simulation trajectory yielded important insights regarding the DNA quadruplex, indicating its properties under different physiological conditions. These findings could be helpful for further studies on the interaction of DNA quadruplexes with external agents and ligands, contributing to a better understanding of their interaction capabilities.
Keywords: G-quadruplex telomere, MD simulation, Torsional and Helicoidal parameters, Non-canonical DNA, Oxytricha trifallax, X3DNA.
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