ADL: Docked binding energies - how accurate are they?

Meg multanova at
Thu Nov 3 17:59:41 PDT 2011

Hi all,

I have a question about the binding energies that come out of autodock

I have a sugar-cleaving enzyme, and I have docked a known inhibitor
(monosaccharide analog) and a trisaccharide (the substrate) to its active
site.  I made all non-redundant bonds rotatable.  I am getting the
following results for binding energies:

Inhibitor: -5.5 kcal/mol (equates to 130 micromolar affinity)
--- The wetlab-determined Ki is 50 micromolar  (so, within a similar range)
Trisaccharide substrate: -7.5 kcal/mol (equates to 5 micromolar affinity)
--- However, the wetlab-determined Km is 1 millimolar. (3 orders of
magnitude away)

I'm calculating the affinity using Gibbs' Free energy equation, as AutoDock

The fact that the trisaccharide is a substrate, and therefore I'm expecting
to see some conformational change upon binding, may relate.  I was
surprised though that the difference (micromolar to millimolar) was so
big.  Could the size of the ligand relate to the accuracy of the binding
calculation?  Have any other people seen this?

Does anyone have insight onto what I can make of this?

Thanks in advance,

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