Experimental research on nucleic acids has shown that guanine-rich regions have the capability of folding into secondary structures known as G-quadruplexes. When found in mass quantities, these structures have the potential to bind to non-RNA binding proteins in the cytoplasm of cells, disrupting many important interactions between proteins and nucleic acids, leading to gene expression misregulation. In particular, a hexanucleotide repeat ((G4C2)n) expansion of RNA has been linked to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease and Parkinson’s disease. The aim of this study was to study a stable, low-energy, parallel conformation of an RNA G-quadruplex with the sequence (G4C2)4. Molecular Operating Environment (MOE) and Visual Molecular Dynamics (VMD) were used in creating the first computational model of the RNA G-quadruplex. Further molecular dynamic and metadynamic simulations were performed using NAnoscale Molecular Dynamics (NAMD) in order to equilibrate the system and determine the free-energy landscapes of the structure in KCl and MgCl2. The free-energy landscapes show lower free-energy basins for the G-quadruplex and hairpin structures.

RNA G-quadruplex topology and stability

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.