Nucleic acid structures are stabilized by both base pairing and base stacking. While energetics of base pairing interactions are relatively well established, our understanding of the energetic contributions of base stacking remain incomplete. Here, we use a combination of single-molecule and computational biophysics approaches to investigate the effect of strand polarity on base-stacking energetics. We designed pairs of DNA constructs with reversed stacking polarities at nick sites, along with corresponding no-stack controls to isolate stacking contributions. Performing single-molecule force-clamp assays with a Centrifuge Force Microscope (CFM), we observed polarity-dependent differences in stacking energetics. These differences were most pronounced in purine–purine and certain purine–pyrimidine interactions. Notably, a 5′ purine stacked on a 3′ pyrimidine was generally more stable than the reverse polarity. We employed molecular dynamics (MD) simulations to observe stacking interfaces in the DNA constructs. The simulations were qualitatively consistent with our experiments, and showed positional differences between opposite polarity stacking pairs, giving some insight into the origin of these polarity differences. Overall, these results demonstrate that base polarity can modulate stacking stability and should be considered when designing short duplex regions such as overhangs in molecular biology and biotechnology applications.

Governor Hochul announced a $50 million capital investment by New York State to expand the State University of New York at Albany’s RNA Institute.

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UAlbany scientists at the RNA Institute are seeking to understand the molecular mechanisms that drive disease. Kaalak Reddy’s team was recently awarded $420,000 from the Eunice Kennedy Shriver Nationa...

ALBANY, N.Y. (WRGB) — In recognition of International Myotonic Dystrophy Awareness Day, landmarks across the state, including Empire State Plaza, were illuminat

The RNA Institute welcomed over 200 attendees to its annual “World RNA Day” celebration. Festivities included lab tours and research presentations to showcase how studying RNA’s structure, function an...

Shenglong Zhang is breaking new ground in understanding how RNA shapes health, with a focus on sequencing RNA modifications that give rise to disease. Zhang recently received $1.6 million from the Nat...

Eight winners of the 2025 Chancellor's Awards for Student Excellence reflect on the UAlbany careers.