Our recent improvements to atomic force fields led us to ask: Is MD accurate enough to predict DNA origami structure? The pointer structure, studied via cryo-electron microscopy (cryo-EM), is currently the best-characterized DNA origami object. We found during a 200 ns simulation of an atomistic model of the pointer starting in idealized conformation, the DNA origami object rapidly approached a conformation consistent with the cryo-EM reconstruction.
The all-atom model of the origami object was large (~6 M atoms), and the simulations were performed over months on hundreds of supercomputer nodes. This limits the utility of the method for routine structure prediction, an important goal in the field of nanotechnology. Hence, we developed an alternative approach that neglects solvent and long-range electrostatics, utilizes an elastic network of restraints to stabilize the DNA, and uses additional restraints to spread the DNA helices away from origami crossovers.
The elastic-network guided simulation worked extremely well. In just 2 nanoseconds of simulation, the DNA conformation approached a conformation consistent with the cryo-EM reconstruction (see trajectory on nanoHUB). Such a short simulation can be performed on a workstation. To validate the all-atom simulation protocol, the elastic-network guided structure was submerged in solvent and simulated for ~150 ns. The structure was seen to be stable.
MD simulation accurately captures subtle structural features of DNA origami. For example, the characteristic chickenwire pattern observed in experiment emerges in our simulations. Unusual motifs, such as the left-handed psuedo-helix are realistically modeled. Hence, if atomically-detailed structure prediction is needed, MD simulation is the method of choice. Setup your own origami structure prediction simulation here!