E-state modeling of dopamine transporter binding. Validation of the model for a small data set.
Data for 25 tropane analogues binding to the dopamine transporter were modeled using E-state molecular structure descriptors. Both E-state and hydrogen E-state descriptors appear in the model in both atom-level and atom-type descriptors. A statistically satisfactory four-variable model is obtained, and structure interpretation is given for each variable, emphasizing substituent influence on nonpolar parts of the molecule as well as the role of hydrogen bonding. A leave-group-out approach to model validation is presented in which each observation is removed from the data set three times in random groups of 20% of the whole data set. The average of the resulting predicted values constitutes consensus predictions for these data and supports the claim that the E-state model may be useful for prediction of pIC50 values for new compounds.
Maw
H H
HH
Department of Chemistry, Eastern Nazarene College, Quincy, Massachusetts 02170, USA.
Hall
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LH
D002352:Carrier Proteins / Q000378:metabolism*; D016208:Databases, Factual; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008954:Models, Biological; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D014326:Tropanes / Q000378:metabolism
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014326:Tropanes; D004298:Dopamine