Since the invention of ligand
efficiency (LE) more than two decades ago, scholars have been debating its
strengths and weaknesses. And alternatives; we've written about LLE, LLEAT,
LELP, %LE, WTF, and more. Just last week we discussed CRE.
But all these metrics (with perhaps one exception) have a problem: they sometimes tell you that your molecule is not as good as you hoped.
And who wants to hear that?
Maybe you used cutting-edge AI technology to design your ligand, and then moved heaven and earth to make it.
When you finally test it the result comes back - meh. But that doesn't mean the
haters should win!
You can't (or really shouldn’t)
change the assay results, but you can change the scoring system, and now
researchers at the University of Durak have come up with a new metric called
NICELE (No Insulting Critical Evaluation Ligand Efficiency). Unlike xLE, the
calculation is simple:
NICELE = LE + F, where F = (1.0 - LE)
Let's say your fragment comes in
with a LE of 0.18 kcal/mol per non-hydrogen atom - not so good. That's OK, the
NICELE is a much more impressive 1.0!
As a bonus, because LE is removed
from the final calculation, NICELE is independent of standard state
assumptions, so Dr. Saysno should embrace it.
Of course, NICELE makes it
harder for those molecules with truly impressive ligand efficiencies to stand
out, but they're a bunch of elitists anyway.
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