A new approach to radial basis function approximation and its application to QSAR.
We describe a novel approach to RBF approximation, which combines two new elements: (1) linear radial basis functions and (2) weighting the model by each descriptor's contribution. Linear radial basis functions allow one to achieve more accurate predictions for diverse data sets. Taking into account the contribution of each descriptor produces more accurate similarity values used for model development. The method was validated on 14 public data sets comprising nine physicochemical properties and five toxicity endpoints. We also compared the new method with five different QSAR methods implemented in the EPA T.E.S.T. program. Our approach, implemented in the program GUSAR, showed a reasonable accuracy of prediction and high coverage for all external test sets, providing more accurate prediction results than the comparison methods and even the consensus of these methods. Using our new method, we have created models for physicochemical and toxicity endpoints, which we have made freely available in the form of an online service at http://cactus.nci.nih.gov/chemical/apps/cap.
CADD Group, Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health , DHHS, NCI-Frederick, , 376 Boyles St., Frederick, Maryland 21702, United States.
Alexey V
AV
Zakharov
Megan L
ML
Peach
Markus
M
Sitzmann
Marc C
MC
Nicklaus
D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D003530:Cyprinidae / Q000502:physiology; D003621:Daphnia / Q000187:drug effects / Q000502:physiology; D016208:Databases, Factual; D020407:Internet; D008954:Models, Biological; D016571:Neural Networks, Computer; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D012984:Software; D013768:Tetrahymena / Q000187:drug effects / Q000502:physiology; D018675:Toxicity Tests