Many, many moons ago Mike Hann at GSK published a paper that is either the most cited paper in FBDD, or should be (Hann et al. J. Chem. Inf. Comput. Sci. (2001) 41: 856). In it, he presented a simple, but quite useful, model of binding.
The whole point of this model is it illustrates how less complex ligands (fragments)have a better probability of binding productively, but more importantly have less chance of having a detrimental binding event (the dreaded +/+ or -/- in this model).So, in this case, atoms are like apples, one bad one ruins the whole bunch.
As has been pointed out previously on this blog, the magic methyl is fleeting and may not even exist. But it has unitary power that makes everyone seek it, like the One Ring. So, in my neverending quest to generate new terminology (e.g. Fragonomics) and be entertaining, if not informational, I would like to coin the term "Sauron atom" for that one bad atom that can cause a fragment not to bind.