Chemistry Reference
In-Depth Information
computational rescoring and perform deep analysis of molecular annotations
during virtual screening pipelines workflows.
A more efficient management of the large volume of chemoinformatic
workflows/procedures may require the usage of manager Pipelines in order to
speed-up the discovery of new bioactive compounds. Depending on the purpose
there are continuously new conceived computer-aided drug design procedures as
well as databases with advantages and drawbacks.
Molecular docking can be rationalized as the exploration for accurate ligand
conformations and orientations within a given biological target that benefits when
using single conformer databases. This procedure reduces computational time in
calculating conformers during the screening as well as the pre-parameterization of
docking runs before virtual screening campaigns.
With the development of new software and crystallographic structures yielding
adequate pharmacophore hypothesis, we are witnessing a rebirth, going back to
several decades of pharmacophere modeling (allowing screening of millions of
compounds in shorter times).
We note that pharmacophores are three-dimensional representation of molecular
features needed for binding to a biomolecule. The ligand conformation plays an
important role for the matching of ligands with pharmacophore hypothesis. It may
be necessary to pre-calculate the probable conformational states of the ligands,
taking advantage of ready-to-use databases or use online computational tools.
The usage of online tools could make it possible for the end-user to screen very
large number of compounds, downloading and further analyzing only small hit
lead sets. Another potential future trend lies in the virtual screening of molecules
for which many companies offer synthesis-on-demand as well as molecules that
can be easily obtained in a few steps of chemical synthesis (tangibles),
It is well known that the complete chemical space is about 10
60
organic
compounds making impossible the creation of a comprehensive database. There
are not sufficient corresponding free
de novo
databases although billions of
compounds have been already analyzed. These efforts are also blunted by the
