| The
use of in silico prediction of
ADME/Tox properties is gaining acceptance
as a useful assessment tool for early identification
of likely drug candidate failures. However,
until now, it has been difficult to locate
reliable models for the prediction of human
pharmacokinetics in silico.
This Volume of Distribution
model predicts the total distribution volume
available to a drug in the body. Low volumes
of distribution imply that the drug remains
in the plasma while very high volumes indicate
that the drug distributes widely into the
various tissue compartments in the body.
In the Strand Volume
of Distribution model, developed by Strand
Genomics, several machine-learning methods
including neural networks, decision trees
and support vector machines were employed
to identify a small set from 1054 molecular
descriptors that correlated with this pharmacokinetic
parameter.
The input to the
predictors is the 2-D structure of a molecule,
which is used to compute the descriptors
that are utilized by the models. Structures
may be imported as either SMILES, MOL, SYBYL MOL2 or SD
files.
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