Free Energy Calculations and Ligand Binding - scc.acad.bg

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Figure 8. Stereo view of the predicted (MD average) binding conformation of an
active inhibitor (top, rightmost in Fig. 7; green) in complex with Plm II (yellow),
superimposed on the X-ray structure of pepstatin A (purple) complexed with Plm II
(light blue) (Silva et al., 1996).

Figure 9. Schematic representation of the specificity sub-sites on serine proteases and
their inhibitors/substrates as introduced by (Schechter and Berger, 1967).

Figure 10. Scatter diagram of calculated vs experimental binding free energies
(kcal/mol) of trypsin-BPTI complexes relative to P1-Gly (Brandsdal et al, 2001b).
The correlation coefficient obtained was 0.99 with a mean unsigned error of 0.38
kcal/mol.

Figure 11. Calculated versus observed binding free energies for nine ligand complexes with
P450cam obtained from LIE calculations (Almlöf et al., 2003), using the earlier
parametrization of Eq. (13) (Hansson et al., 1998), but with a constant term of γ = −4.3
kcal/mol. Three different force fields were used: (A) Gromos87, (B) OPLS-AA and (C)
Amber95.

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Figures
Figure 1

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Figure 2

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Figure 3a
Figure 3b

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Figure 4

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Figure 5

D2d + N+ ∆∆Gbind Experiment
[kcal/mol] Amber95
+ N Gromos87
4
N WATER
S4 3
N+
+ 2

N 1

D2d + + 0
TMA
+ N N
CHANNEL
N N+

S4 +

N

TEA TPA

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Figure 6