Last revision: 19-01-2012 

*The model compounds presented in this directory contain the atomic
charges of GROMOS 43A1 force field and the pKmod values from Tanford
(ref[1]).

*The files HIStau1.st and HIStau2.st contain the pKmod values in
ref[2] instead.

*The files H2Oxxxx.st, HOHxxxx.st, SERxxxx.st, and THRxxxx.st have
 very low pKmod values (-100). These sites are not meant to titrate
 but can exhibit different proton isomers that should be taken into
 account. Thus, the presence of those files.

*The files corresponding to the different proton isomers (tautomers)
contain "tau" in their designation (e.g. TYRtau1.st and TYRtau2.st).
Bear in mind that the pKmod of each tautomer is different from the
global pKmod (check ref[3] and ref[4] for more details).

*If you do not wish to include tautomers in your calculations, use the
files containing either "all" or "avx" in their names (e.g. TYRall.st
or TYRavx.st). 

"all": These files choose the proton isomer that appears in
the force field and present the global pKmod of the site.

"avx": These files follow the approach of spreading an average charge
among the selected atoms and present the global pKmod of the site. 
 
*The pKmod in ARGtau files was calculated assuming that the four
tautomers are equiprobable. This is not correct due to the lack of
symmetry of the guanidyl site. The lack of information about the
neutral forms of this site does not allow us a better approach. Also
the correct charge distribution in the neutral forms is a matter of
concern. For these reasons, you should consider using ARGavx.st.

*The files with the prefix CTALA, corresponding to the C-terminus of
alanine, can be easily transformed in any other type of C-terminus by
simply substituting all occurrences of "ALA" (in the name of the files
and inside the files) by any other residue name. 

E.g. The C-terminus site of leucine can be created like this: 
sed 's/ALA/LEU/g' CTALAall.st > CTLEUall.st

Actually, something like this is done by the getst program included in
the meadTools package. The same applies to the N-terminus sites that
can be created from the files with prefix NTALA.
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ref[1]: Nozaki, Y, Tanford, C (1967) "Examination of titration
behaviour" Methods Enzymol, 11, 715.

ref[2]: Bashford, D, Case, DA, Dalvit, C, Tennant L, Wright PE (1993)
"Electrostatic Calculations of Side-Chain pKa Values in Myoglobin and
Comparison with NMR Data for Histidines" Biochemistry, 32, 8045.

ref[3]: Baptista, AM, Soares, CM (2001) "Some theoretical and
computational aspects of the inclusion of proton isomerism in the
protonation equilibrium of proteins" J Phys Chem B, 105, 293.

ref[4]: Machuqueiro, M, Baptista, AM (2011) "Is the prediction of pKa
values by constant-pH molecular dynamics being hindered by inherited
problems?" Proteins, 79, 3437.
