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11. Prediction of pKa's - JOBTYPE pK
JOBTYPE pK
calculates the pKs of ionizable sidechains in the TEMPLATE
structure. Ionizable groups in proteins have pK's that are often
shifted from model compound values (Figure 11.1). The
magnitude of the shift from model compound pKs is directly coupled to
the electrostatic energy of the group, and is a sensitive probe of the
local electrostatic environment (Figure 11.2). The
accuracy of pK predictions made using the Generalized Born model within
EGAD is reasonable, and gives a similar level of accuracy as
Poisson-Boltzmann methods (Figure 11.3; Pokala and Handel 2004).
SCMF calculations are done as a function of pH (1.0 -> 13.5 every
0.25 pH units). Unlike other jobs, both protonated and deprotonated
rotamers are explicitly considered for ionizable residues.
The fraction charged for each residue at each pH is listed in the output_prefix.titr file:
pH
residue_id(1) . . . residue_id(n)
total_charge_of_molecule predicted energy
After the titration is completed, the output_prefix.pK
file lists the apparent pKs:
seq_position
residuetype
pK ∆pK (with respect to
model compound pK in resparam file)
The apparent pK is defined as the pH at which the protonated and
deprotonated rotamers for a given residue have an equal self-consistent
mean-field probability (0.50 in the .titr file). The apparent pK is estimated by
linear interpolation between the pH steps flanking the Pcharged
= Pneutral = 0.5 point.
In some cases, a residue's pKa is impossible to calculate (especially
lys and tyr); these are indicated with not_titr.
For an example, see examples/pK/barnase.pK.input and the
resulting output files.
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