[AMBER] protonation of protein-ligand complex

From: Thomas Evangelidis <tevang3.gmail.com>
Date: Thu, 14 Nov 2013 21:30:45 +0200

Dear AMBER community,

I am simulating a protein-complex in which protonation of two glutamic
acids in the binding pocket is believed to dictate ligand binding and
release. I want to calculate pKa values from conformations along the
simulation and change if necessary the protonation of the protein by also
taking into account the ligand. I used for this purpose PROPKA 3.1 and H++
servers, but the results are contradictory. According to PROPKA 3.1 the pKa
values of the two Glu residues in the starting conformation are 8.07 and
7.61, therefore in pH 7.6 both will be protonated. According to the
titration curves produced by H++ these two residues are never protonated at
pH 7.6 whatever dielectric I use for the protein (tried values 1-10). It is
worth noting that the titration curve of the first Glu deviates a lot from
the Henderson-Hasselbalch curve.

I am confused about what results I should trust. Is there a program in
AmberTools to calculate pKa values and protonate by taking into account the
effect of the ligand? I found in the manual a program named calcpka but I
cannot understand the arguments it takes. Is there any other tool that you
would recommend for that purpose?

thanks in advance,

Thomas Evangelidis
PhD student
University of Athens
Faculty of Pharmacy
Department of Pharmaceutical Chemistry
157 71 Athens
email: tevang.pharm.uoa.gr
website: https://sites.google.com/site/thomasevangelidishomepage/
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Received on Thu Nov 14 2013 - 12:00:03 PST
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