Structure-based validation of the 3D-QSAR technique MaP.
For three target proteins with different binding pocket characteristics (size and shape, hydrophobicity, hydrogen-bonding) a structure-based validation of the translationally and rotationally invariant 3D-QSAR technique MaP is performed (MaP: Mapping Property distributions of molecular surfaces). The structure-based validation procedure comprises two steps: first, QSAR models are derived without using the information of the target protein. Second, the models are back-projected into the crystal structure of the binding pockets and interpreted. It is demonstrated that MaP is able to identify characteristics important for ligand binding in the cases studied here. Moreover, it is demonstrated that MaP is a versatile 3D-QSAR technique since good, predictive models could be obtained for all three data sets showing distinct characteristics.
Stiefl
Nikolaus
N
Department of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, D 97074 Wuerzburg, Germany. knut.baumann@mail.uni-wuerzburg.de
Baumann
Knut
K
D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D011506:Proteins / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry
D002800:Cholinesterase Inhibitors; D011506:Proteins; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase