Investigation of DNA aptamer modifications associated with glioblastoma through moleculer modeling

Abstract

Objectives: In adults, Glioblastoma (GBM) is the deadliest primary brain tumor in the central nervous system. Aptamers, single-stranded oligonucleotides, interact with their target molecules through precise structural interactions. Aptamer modification invol ves intentionally introducing chemical or structural changes to enhance their specificity and effectiveness in binding with their intended targets. These delibe rate modifications aim to amplify aptamers’ binding affinities, overall stability, or target specificity. Methods:The aim of our study is to investigate DNA aptamers known to be effective in diseases such as glioblastoma by subjecting them to various modifica tions and conjugations and determining their binding efficacies through molecular dynamics simulations. To achieve this goal, we obtained the structures of these aptamers from the Aptagen database and pre pared each aptamer for chemical modifications and conjugations using the CHARMM-Gui. Subsequent ly, we conducted molecular dynamics simulations of each modified DNA aptamer and aptamer-protein interaction in GROMACS and examined the structu ral changes before and after modification using the VMD program. The Xmgrace program was utilized for data analysis. Results:Our findings have revealed that modificati ons applied to specific aptamers lead to significant alterations within their respective binding regions, resulting in a reduction of binding efficacy for certain aptamers while enhancing it for others. These varia tions have exerted diverse effects on the interactions between aptamers and the target molecules, thereby exerting a nuanced influence on their selectivity cha racteristics. Conclusions: In summary, our findings suggest that further research is warranted to explore the potential of DNA aptamer modification and conjugation as in novative diagnostic and therapeutic tools for diseases such as GBM