Chemistry Reference
In-Depth Information
Table 3 The apparent pK
a
of titrating acidic groups in calbindin D
9k
. Exper-
imental and various theoretical results. The 'low dielectric' results of
Spassov and Bashford are highlighted. Both Spassov and Bashford
13
and Juffer and Vogel
14
have used the DH approximation, but the latter
authors have assumed a uniformly high dielectric permittivity in the
same way as Kesvatera et al.
12
The r.m.s. deviations are given in units
of pK
a
pK
a
(experiment)
pK
a
(theory,
ref. 13)
pK
a
(theory,
ref. 14)
pK
a
(theory,
ref. 12)
Residue
Glu-27
6.5
21.8
5.2
4.7
Asp-54
3.6
16.9
4.8
4.4
Asp-58
4.4
9.1
4.8
4.8
Glu-60
6.2
13.2
5.6
6.0
Glu-65
5.4
12.7
4.6
5.0
r.m.s.
-
10.6
0.93
0.92
Kesvatera et al.
12
also contains results from MC simulations using a uniform
dielectric response equal to that of water. Obviously, the calculations using
a low dielectric interior containing charged groups are unable to describe the
electrostatic interactions in calbindin and the results are unphysical.
9.4 Interaction of Two Charged Macromolecules
9.4.1 Interaction of Two Peptides
Calmodulin binds to myosin light chain kinase (MLCK) via a small peptide that is
rich in basic residues. Calmodulin and the peptide form a complex which has been
isolated and crystallized. Let us remove from this complex the peptide, smooth
muscle MLCK (
ΒΌ
smMLCK), and study the interaction between the pair. The
netchargeofsmMLCKatneutralpHiscloseto+7e and the two peptides repel
each other, i.e.,thefree energy of interaction is positive [Figure 5(a)]. The
unscreened direct electrostatic interaction between the peptides is, of course,
strongly repulsive, but the total electrostatic energy, including the background
electrolyte, is essentially zero or sligthly attractive for all separations. Thus, the
repulsion between the equally charged peptides is totally dominated by the
entropy - the entropy of the salt and counter-ions. An increase in salt concen-
tration from 4 to 100 mM does not change this picture, as shown in Figure 5(b).
A different picture emerges for the interaction of two oppositely charged
peptides. Figure 6 shows the free energy of interaction between smMLCK and
a peptide section from calmodulin comprising Glu45
Glu67 with a net charge
of
8e. The interaction free energy is strongly attractive and so is the total
energy. Thus, the attraction is energy driven and the entropy change is in this
case only marginal.
The interaction between two charged macromolecules in a salt solution is
screened by salt particles. One can derive an expression for the free energy of
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