I've never run mine on one cylinder to set the idle mixture screws, but disconnecting the plug while the engine is not running is the way to do it. I find that setting the idle screws for highest RPM is easy enough by watching the tach while both cylinders are firing.
If you do run it on one, for the sake of the spark coil, connect a spare plug and lay it on something grounded, rather than letting the plug cap arc to something an inch away.
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