Subject: MEAD pKa calculations

From: "CUI, Guanglei" <[email-masked]>
Date: Sun, 9 Feb 2003 16:46:34 -0500 (EST)

Dear CCL readers, 
     I'm trying to use MEAD to calculate pKa of three residues in a
     ligand binding site. The structure has been minimized with AMBER
     force field with explicit solvent. The charges of these residues
     have been derived from RESP calculations. All needed files are
     created and multiflex calculation used epsin = 4.0. After the
     calculation, the intrinsic pKas of two residues are very
     surprising. So here's my questions:

     1. What could be reasons that the self interactions for residue UNK
     and LYS are very big. 
     2. During the multiflex calculation, I was warned of "vertex
     found with count = 2" three times. How should I deal with this? 
     3. Do I need to include explicit solvent molecules in the
     calculation, generally speaking? The binding site is not completely
     buried. 
     4. LYS (protonated) has 3 equivalent hydrogens. It's not very clear
     to me which one should be zero charged in LYS.st file. 
     
     Here're the .summ file. Sorry for the lengthy description. Any
     suggestions are welcome. Thanks in advance. 

   site name           pKmod      delta self    delta back      pkint
       UNK-259           7.8       23.1134      -5.41211       25.5013
       LYS-162          10.4      -11.4993       1.32968        0.23042
       TYR-155           9.6      0.694971      -1.28149        9.01348

-- 
Guanglei Cui
Dept. of Chemistry
SUNY at Stony Brook
Stony Brook, NY 11790