The objective of this study was to computationally characterize 10 RNA duplexes containing 3' overhangs that are involved in the RNAi mechanism. The 10 systems were previously examined by Serra and coworkers using melting point studies. Molecular dynamics simulations of 10 3’ overhangs on a GGCC core were performed for 100 nanoseconds each at 200 mM and 1 M NaCl ion concentrations. RMSD calculations indicated low deviations from both starting and average structures suggesting a well-equilibrated system. RDF calculations of the 1 M system confirmed non-aggregating sodium and chloride ions. Base stacking plots revealed the pyrimidine-purine overhangs rotated out into solution rather than stacking over the RNA core. The purine-pyrimidine and purine-purine overhangs showed strong stacking interactions with the first 5’ base of the core. Free energy calculations using the generalized born and poisson Boltzmann models in the mmpbsa.py suite of Amber are planned. The conclusions drawn from this work will give insight into the way in which Dicer recognizes favorable overhang sequences in long dsRNA segments.

Computational study examining the stability of 3’ overhangs in the RNAi mechanism

251st National Meeting (2016)

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