Development of prediction model for fructose- 1,6- bisphosphatase inhibitors using the Monte Carlo method

• Published in: SAR and QSAR in environmental research Vol. 30; no. 3; pp. 145 - 159
• Main Authors: Manisha, Chauhan, S., Kumar, P., Kumar, A.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.03.2019; Taylor & Francis Ltd
• Subjects: Calibration; Computer simulation; CORAL; Diabetes mellitus; docking; Drug development; Enzymes; FBPase; Fructose; Gluconeogenesis; Inhibitors; Liver; Mathematical models; Molecular docking; Monte Carlo simulation; Parameters; Prediction models; QSAR; SMILES; Structure-activity relationships; docking; SMILES; CORAL; FBPase; QSAR
• ISSN: 1062-936X; 1029-046X; 1029-046X
• DOI: 10.1080/1062936X.2019.1568299

Fructose-1,6-bisphosphatase (FBPase) is an enzyme important for regulation of gluconeogenesis, which is a major process in the liver responsible for glucose production. Inhibition of FBPase enzyme causing blockage of the gluconeogenesis process represents a newer scheme in the progress of anti-diabetic drugs. The current research describes the development of hybrid optimal descriptors-based quantitative structure-activity relationship (QSAR) models intended for a set of 62 FBPase inhibitors with the Monte Carlo method. The molecular structures were expressed by the simplified molecular input line entry system (SMILES) notation. Three splits were prepared by random division of the molecules into training set, calibration set and validation set. Statistical parameters obtained from QSAR modelling were good for various designed splits. The best QSAR model showed the following parameters: the values of r 2 for calibration set and validation set of the best model were 0.6837 and 0.8623 and of Q 2 were 0.6114 and 0.8036, respectively. Based on the results obtained for correlation weights, different structural attributes were described as promoter of the endpoint. Further, these structural attributes were used in designing of new FBPase inhibitors and a molecular docking study was completed for the determination of interactions of the designed molecules with the enzyme.