Chemistry Reference
In-Depth Information
(a)
(b)
5000
4000
3000
2000
1000
0
0
2
4
6
8
RMSD to Target
Figure 5.6
(A) COST versus the RMSD (Å) to the target pose for CDK2-/
4
. The predicted
protein chemical shifts were set to the corresponding BMRB average values. The 3D X-filtered
NOESY spectrum used as input for NOE matching was simulated from the target structure.
(B) Superposition of target pose and the minimum cost pose (dark gray) from (A).
the simulated 'experimental' chemical shifts. The simulated NOE list for this complex con-
tained a total of 110 peaks, which were clustered into 53 protein
1
H
13
C groups. Trial binding
poses were generated with
Poser
. The compound binding site was defined as the active site
of the protein; the 'posing box' was expanded by 1 Å in all coordinate axes. For each of
the five ligand conformers (generated with Omega), 629 669 376 poses were generated
and evaluated by
Poser
, with 45 693 poses being retained. The RMSDs of the retained trial
poses to the target pose ranged from 0.64 to 7.56 Å. The NOE matching protocol was run
using BMRB-predicted chemical shifts.
The results obtained fromapplyingNOEmatching to FKBP-12/
5
are shown in Figure 5.7.
The pose with the minimum COST value has an RMSD of 0.64 Å to the target pose; this
pose also had the lowest RMSD of all 45 693 with respect to the target pose.
(a)
(b)
7000
6000
5000
4000
3000
2000
1000
0
0
2
4
6
8
RMSD to Target
Figure 5.7
(A) COST versus the RMSD (Å) to the target pose for FKBP-12/
5
. The predicted
protein chemical shifts were set to the corresponding BMRB average values. (B) Superposition
of target pose and the minimum cost pose (dark gray) from (A).
