Subject: Delphi pk calculation

From: Troy Wymore <[email-masked]>
Date: Tue, 18 Jul 2000 18:25:48 -0400 (EDT)

Hello Delphi experts,

I am attempting to calculate pK shifts in an active site cysteine residue.
To carry out the calculation, I have largely followed the examples in
Delphi version 3.0 on histidine in trypsin and explanations laid out in a
paper by Yang et al. "On the calculation of pKas in proteins" PROTEINS,
1993, 15:252-265.  I start out using a box fill of 20% and dipolar
boundary conditions and then focussing in three steps to 90% box fill.  My
reaction field energies converge in the last two calculations. No problem
with dG(solv)
  
When I do the same analogous procedure to get the dG(dipoles + charges),
my total energies from the bottom of the frc file are not converging and
they totally dominate the result. 

For charged cysteine with partial charges on the protein:
56.93215 kt
For neutral cysteine with partial charges on the protein:
28.74323 kt

I am using PARSE3 sizes and CHARMM charges and I center the active site
residue before doing the calcs.

Should the total energies converge at larger box fills? Should they be so
large?  Perhaps I should try using a minimized structure instead of the
x-ray coordinates.

Any help on this would be much appreciated.

Troy Wymore
Pittsburgh Supercomputing Center