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Applications of Polypharma Database |
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Polypharma is a dedicated database for the
multi-targeted ligands and targets. The highly accurate structural and activity
(both binary and continuous) could be used to develop various ligand-based
(e.g., QSAR) to predict off-targets or design polypharmacological agents. We are in the process of developing new and novel algorithms to predict
the off-targets from the available activity data. Similarly several structure-based methods/models like docking/inverse docking can be used
to identify new off-targets or candidate compounds |
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Ligand-based prediction of targets
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Correlating the ligand properties to binary binding fingerprint
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As shown in below, binary binding data describing the ligand-target
interactions can be obtained from the Polypharma
database. For example, ligand L1 binds to a specific set of
targets (E.g. Targets 1,3,..,n).
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T1
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T2
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T3
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T4
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.
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.
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Tn
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L1
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1
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0
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1
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0
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.
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.
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1
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L2
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0
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0
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1
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1
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.
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.
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0
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L3
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1
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1
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0
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1
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.
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.
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1
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..
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..
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Lq-1
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1
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0
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1
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1
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0
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Lq
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?
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?
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?
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?
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?
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Form the binary binding
information of the all the ligand-target interactions, new interaction pairs
can be predicted for a query ligand (Lq) using
ligand-based (QSAR) approaches. The structural information of the ligands (physico-chemical descriptors) can be mapped to the binding
fingerprint patterns to predict the binding fingerprint of the query ligand.
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Correlating the ligand properties to multi-target activity data
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In the same lines discussed above, the ligand structural
information can also be mapped to continuous activity data (e.g. pKa ), and the possible
real activity against a set of targets for the query ligand can be predicted.
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T1
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T2
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T3
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T4
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Tn
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L1
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1.0
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4.0
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-
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3.0
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0.1
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L2
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3.0
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4.7
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9.0
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-
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0
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L3
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1.1
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-
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-
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3.4
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5.2
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..
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..
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Lq-1
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3.8
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-
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1.2
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7.0
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-
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Lq
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?
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Structure-based prediction of targets
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Structure-based methods
including inverse docking are also widely used to predict protein targets of
small molecules. We plan to screen all the polypharmacological targets against
all the polypharmacological ligands and vice-versa using docking
/ inverse-docking approaches. The targets/ligands with available 3D structures
deposited in this database would used. For a given ligand, the top ranked
targets (excluding the original known targets) can be treated as the lead
off-targets and can be further considered for testing.
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