We routinely run our ligands through DFT QM using
Gaussian. While conformations 'in vacuo' are not very helpful for a real
structure, bond lengths and angles are at least as accurate as they can be
without going to small-molecule crystal structures.
A.G.E.
----- Original Message -----
Sent: Friday, November 15, 2002 6:46
PM
Subject: Re: [ccp4bb]: Comments on
ligands
I agree w/ much of what Phil and
Jim have said well.
RE: NADPH, I was
amazed how difficult it was to address the geometry of the nicotinamide ring
at 1.05 A resolution (entry 1KMS). We consulted HICCUP and the PDB (CSD was
also very helpful), both of which helped some. But, ultimately, common
chemical sense prevailed...if it's a C=C double bond, the bond length is
so-and-so, if it's a C-C single bond, it's longer, etc. (I am sure that the
French group which has aldose reductase w/ NADP(H) at 0.6 A will set us all
straight!)
I find that the (Refmac,
CNX, etc.) dictionaries can often be inadequate/questionable/wrong. GIGO. And
be careful.
Also, remember that it is
energetically very costly to distort bond lengths, somewhat less so bond
angles, and torsion angles can be fiddled with almost with impunity (though
staggered is preferred). So if you see in a PDB entry a ligand where the
phenyl ring substituent comes off at 110 degrees, it is probably wrong. If
that C-C bond is 1.65 A, it is probably wrong. If the Mg-O distance is 2.9
instead of 2.2 A, maybe it is a water, not Mg. (I could continue...but
won't!)
And yes, Gerard is
right...deposit theose SF's!
Dave ~~~~~~~~~~~~~~~~~~~~~~~~ David Borhani Group Leader,
Biochemistry Vox: 508-849-2944 Fax:
508-755-8361 Email:
david.borhani@abbott.com Smail: Abbott
Bioresearch Center, Inc. 100 Research
Drive Worcester, MA 01605
U.S.A. ~~~~~~~~~~~~~~~~~~~~~~~~
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