Molecular Modeling of Antisense Oligonucleotide Analogs

Antisense oligonucleotides (ASOs) are short, synthetic nucleic acids designed to specifically bind to complementary sequences of RNA. They have become powerful tools in research and medicine due to their ability to modulate gene expression through RNase H-mediated target reduction as well as splice modulation. Molecular dynamics simulations and molecular modeling play critical roles in the study, design, and optimization of ASOs. These computational techniques provide detailed insights into the structure, behavior, and interactions of ASOs at the molecular level. Here, we present a summary of the applications of computational chemistry tools in the study of ASOs and discuss the strengths and disadvantages of each approach.