Subject: Magnitude of uncertainty around amine geometry

From: [email-masked] (M Dominic Ryan)
Date: Fri, 5 Dec 1997 08:53:14 -0500

While getting it 'right' is of course the aim here, I wonder if anyone has an
impression of the room temperature impact of these small changes.  It is my
impression that the non-planarity of amide (and other sp2 conjugated) nitrogens
is not far from the planar geometry enthalpically, and that the surface there
is quite flat.

If the surface is indeed quite flat then at room temperature it could
contribute significantly entropically.  Stiffening up that deformation would
have a measurable effect.

Does anyone have a liquid simulation using the corrections Tom Halgren has
talked about (in the carbon-attached hydrogen repoulsive terms) to fix the
limitations Bill Jorgensen has identified in MMFF? It seems to me that this
would answer much of the impact of the non-planar amide nitrogen question.

Even at 0K, a flat surface with very small difference between the two states
might not have much practical impact.

After all, as others have pointed out, the crystal structures are averaged
structures.

-- 
M. Dominic Ryan   (610)-270-6529  SmithKline Beecham Pharmaceuticals 
[email-masked]             King of Prussia, PA