Intro
Another thing that matters a great deal for how easy it is to make a switch switch well, is that there isn’t too big a difference in the amount of base pairs per state.
Switch designs that have a very big difference in numbers of base pairs between states, are generally harder to solve. Meaning that it is generally easier to solve a switch by making a smaller and partial switch than making all the base pairs switch between states. It is more typical for the bots to solve as full moving switches, because they don’t know, when to make tail bases pair up, how to make the one end of the aptamer stable or make the stem long enough for it to be stabilizing.
Strategy
Reward designs that keeps the amount of switching base pairs not too different between states.
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Give + 3 to designs that has less than 5% difference in amount of base pairs between the states
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Give + 2 to designs that has less than 10% difference in amount of base pairs between the states
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Give +1 to designs that has less than 15 % difference in amount of base pairs between the states
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Start penalize for designs that has a bigger than 15% difference in amount of base pairs between the states and penalize increasingly.
This goes for both turn on and turnoff labs. Either state included.
MicroRNA’s are excluded since they obviously 
needs a big difference of switching base pairs between states, due to need to switch between no microRNA in one state and pairing up with most of a 22 nucleotide long sequence in next.
Background article