Chemistry Reference
In-Depth Information
of the synthons, which come together in a single graphical display (see Figure 9.17) found
in the SA component of VLTK. Synthon analysis presents a comprehensive view of the
property space covered by the fragments simultaneously with structural similarity. The
fragments may be chosen based on chemical property coverage rather than solely on some
measure of dissimilarity or cluster membership. The interactive nature of the SA interface
ensures that the user is able to assess quickly the chemical property space covered by
a fragment, compare it with the coverage of previous selections and contrast it with the
chemical diversity of the available universe of fragments. Indicators for the vendor, price
and availability for each fragment are also provided.
Figure 9.17
A snapshot of Synthons Analysis for the primary amine query.
In Figure 9.17, a snapshot of SA for the primary amine query is given. This input to SA
is the output from the RS tool where both the ACD and an internal proprietary database of
fragments were searched.
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As can be seen, a list of 5000 low molecular weight primary
amines are returned as a direct result of the constraints employed in RS. The 5000molecules
were clustered into 1652 sets. The structure of a representative fragment from each cluster
is depicted in the film strip at the bottom of Figure 9.17, sorted by decreasing cluster
size. With each structure is given the unique molecular ID, molecular weight, size of the
cluster and vendor information. In addition to the cluster size, the number of members in
the selected list, termed primary selections, is indicated next to the cluster size. By way
of illustration, the representative molecules for the 25 largest clusters have been selected
as primary fragments. However, for virtual screening all the fragments would be used.
To clarify the data in the film strip, the ACD compound MFCD00211266 has a synthon
