Subject: Energy Minimisation of Proteins in vacuo

From: Richard M Day <[email-masked]>
Date: Wed, 27 Jan 1999 08:23:22 +0000

Hi CCL'ers,

I have been trying for a while to refine a protein structure (from a PDB !)
and try and remove the problems of poor dihedrals (not just due to
function), poor bond lengths, iffy sidechain planarity etc so it can be
used to do rational design, de novo design etc etc.

Now the protein I have to work on is 70Kda or so and to try and do this
work using a solvated model would be fairly mad because I would have to buy
a few extra hard drives for my indy to process it with a newton raphson
type algorithm.  The alternative in literature suggests in vacuo
simulations using energy minimisation (DISCOVER, CHARMM, MAXIMIN whatever)
with a variable dielectric-distance function and with a fiddle factor
dielectric (different authors reckon either 4 or 20). I tried all these
with my protein and it seems to work a lot better at 20 rather than 1 - and
according to the Vriend & Sander WHAT_CHECK for proteins the dihedrals
(according to ramachandran) seem to have become more tightly focussed where
they should be and the side chains more planar, bond lengths seem to be
more like the norm.

Is this a good alternative to solvation or does this technique completely
over-refine the model and make it worse that just using the raw data ?

Any comment would be greatly appreciated, summary as usual.

Best Wishes,

Richard Day.

Cranfield Biotechnology Centre,
+44 1234 750111 x3562