  Due to inherent complexity active transport presents a landmark hurdle for
oral absorption properties prediction. We present a novel approach
carrier-mediated drug absorption parameters calculation based on entirely
different paradigm than QSPR. We capitalize on recently emerged ideas that
molecule activities against a large protein set can be used for prediction of
biological effects and performed a large scale numerical docking of drug-like
compounds to a large diversified set of proteins. As a result we identified for
the first time a protein, binding to which correlates well with the intestinal
permeability of many actively absorbed compounds. Although the protein is not a
transporter, we speculate that it has the binding site force field similar to
that of an important intestinal transporter. The observation helped us to
improve the passive absorption model by adding non-liner flux associated with
the transporting protein to obtain a quantitative model of active transport.
This study demonstrates that binding data to a sufficiently representative set
of proteins can serve as a basis for active absorption prediction for a given
compound.

Quantitative Methods;Biomolecules