Chemistry Reference
In-Depth Information
NetCharge Distribution
80
70
60
50
40
30
20
10
0
-2
-1
0
1
2
3
NetCharge
ChemBridge
ActiveSight
Maybridge
Figure 9.6
Net charge distributions for ActiveSight, ChemBridge and Maybridge fragment
libraries.
Normalized Bond Flexibility Distribution
50
45
40
35
30
25
20
15
10
5
0
0
0.1
0.2
0.3
0.4
0.5
0.6
NormBondFlex
Maybridge
ChemBridge
ActiveSight
Figure 9.7
Normalized bond flexibility (number of rotatable-bonds/total bonds) distributions
for ActiveSight, ChemBridge and Maybridge fragment libraries.
It was interesting to note that the ActiveSight fragments are reminiscent of early internal
modeling efforts to construct a database of scaffolds for virtual design. While the cores
are fairly flat, typically an undesirable feature for a diverse set of drug-like molecules, it
still remains to be seen whether such rigid flat fragments benefit fragment screening and
de novo
design.
The ChemBridge collection of 5213 compounds was rationally selected from their
EXPRESS-Pick Collection,
[
8
]
utilizing Astex's rule of three considerations (MW
≤
300,
HBD
3)
[
12
]
and measures of diversity. ChemBridge has used a
predicted aqueous solubility of greater than 3mM for all selected compounds and can be
≤
3, HBA
≤
3, CLogP
≤
