I don't know of such a program, but I would think that an algorithm that
considered solvent-exposed ionizable residues only (and everything
ionizable in any disordered/missing loops) of a PDB structure, and
applied the typical pKa values of side chains from Thurlkill et al.
(2006) Protein Sci. 15, 1214, the resulting calculated pI would be a
reasonable estimate of the experimental pI of the protein. The
sequence-based pI calculations, while useful, are understandably only a
crude approximation of the true pI. For proteins used in our lab for
which we have actually done the comparison of estimated and measured pI,
I seem to recall about a 0.5 pH unit difference or more.
The main unknowns in this problem is assigning the proper perturbations
to the pKa values of side chains, which will be affected by the
hydrophobicity of the local environment and electrostatic effects. And
defining what is solvent accessible.
Sounds like it could be an interesting interdisciplinary undergraduate
computer science/biochemistry class project. If it hasn't been done
already. Didn't see anything obvious in SciFinder.
Cheers,
___
Roger S. Rowlett
Gordon Dorothy Kline Professor
Department of Chemistry
Colgate University
13 Oak Drive
Hamilton, NY 13346
tel: (315)-228-7245
ofc: (315)-228-7395
fax: (315)-228-7935
email: rrowl...@colgate.edu
On 9/10/2013 12:25 PM, Hargreaves, David wrote:
Dear CCP4bbers,
I was wondering whether anyone knew of a program that would calculate
the pI of a protein based on its structure rather than its sequence
and whether such a calculation might correlate better with the measured pI
Dave
*David Hargreaves*
Associate Principal Scientist
_
AstraZeneca
Discovery Sciences, Structure Biophysics
Mereside, 50F49, Alderley Park, Cheshire, SK10 4TF
Tel +44 (0)01625 518521 Fax +44 (0) 1625 232693
David.Hargreaves @astrazeneca.com mailto:name.surn...@astrazeneca.com
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