I’ve been reading the literature on conformation switching Aptamers. The idea is to perform rounds of selection to find DNA molecules that change their shape or conformation when they bind a target. The main strategy seems to be to select by releasing DNA from a capture particle.

Morse, D. P. Direct Selection of RNA Beacon Aptamers. Biochem. Biophys. Res. Commun. 2007, 359 (1), 94–101 DOI: 10.1016/j.bbrc.2007.05.072.

Nutiu, R.; Li, Y. Structure-Switching Signaling Aptamers. J. Am. Chem. Soc. 2003, 125 (16), 4771–4778 DOI: 10.1021/ja028962o.

The fact that this works suggests something about the mechanism by which DNA Aptamers operate. One of the big questions that comes up in the lab is whether Aptamers are being folded around their target (an induced fit model) or whether they are switching back and forth between a folded and unfolded state even without the target (an equilibrium binding model). The fact that target can force Aptamers off of a capture particle suggests that the induced fit model may be appropriate in some cases.

On the other hand, a capture based selection strategy (Spiga et. al.) seems to fit either model. As long as the confirmation switches back and forth fast enough, an equilibrium model could account for partitioning between a capture particle and solution.

The downside to this strategy is that the particles need to have enough capacity to absorb all of the nonbinding DNA (which may be quite a lot of DNA at the beginning of the selection).

Spiga, F. M.; Maietta, P.; Guiducci, C. More DNA–Aptamers for Small Drugs: A Capture–SELEX Coupled with Surface Plasmon Resonance and High-Throughput Sequencing. ACS Comb. Sci. 2015, 17 (5), 326–333 DOI: 10.1021/acscombsci.5b00023.

Anyway, if you have a favorite conformation switching aptamer selection paper (and who doesn’t?!), maybe leave it in the comments or shoot me an email.