{Reference Type}: Journal Article
{Title}: Combined 4D-fingerprint and clustering based membrane-interaction QSAR analyses for constructing consensus Caco-2 cell permeation virtual screens.
{Author}: Santos-Filho OA;Hopfinger AJ;
{Journal}: J Pharm Sci
{Volume}: 97
{Issue}: 1
{Year}: Jan 2008
{Factor}: 3.784
{DOI}: 10.1002/jps.21086
{Abstract}: A set of 30 structurally diverse molecules, for which Caco-2 cell permeation coefficients were determined, formed the training set for construction of Caco-2 cell permeation models based upon membrane-interaction (MI) QSAR analysis and a new QSAR method called 4D-fingerprint QSAR analysis. The descriptor terms of the 4D-fingerprints equation are molecular similarity eigenvalues, and this set of descriptors is being evaluated as a potential "universal" QSAR descriptor set. The 4D-fingerprint model suggests that Caco-2 cell permeation is governed by the spatial distribution of hydrogen bonding and nonpolar groups over the molecular shape of a molecule. Moreover, a complementary resampling of the original Caco-2 cell permeation training set, followed by the construction of several "clustered" MI-QSAR models, led to a consensus model consistent in interpretation with the 4D-fingerprint model.