Toward the prediction of FBPase inhibitory activity using chemoinformatic methods.

Currently, Chemoinformatic methods are used to perform the prediction for FBPase inhibitory activity. A genetic algorithm-random forest coupled method (GA-RF) was proposed to predict fructose 1,6-bisphosphatase (FBPase) inhibitors to treat type 2 diabetes mellitus using the Mold(2) molecular descriptors. A data set of 126 oxazole and thiazole analogs was used to derive the GA-RF model, yielding the significant non-cross-validated correlation coefficient r(2) (ncv) and cross-validated r(2) (cv) values of 0.96 and 0.67 for the training set, respectively. The statistically significant model was validated by a test set of 64 compounds, producing the prediction correlation coefficient r(2) (pred) of 0.90. More importantly, the building GA-RF model also passed through various criteria suggested by Tropsha and Roy with r(2) (o) and r(2) (m) values of 0.90 and 0.83, respectively. In order to compare with the GA-RF model, a pure RF model developed based on the full descriptors was performed as well for the same data set. The resulting GA-RF model with significantly internal and external prediction capacities is beneficial to the prediction of potential oxazole and thiazole series of FBPase inhibitors prior to chemical synthesis in drug discovery programs.