title: Monte Carlo method based QSAR modelling of natural lipase inhibitors using hybrid optimal descriptors.
abstract: Obesity is one of the most provoking health burdens in the developed countries. One of the strategies to prevent obesity is the inhibition of pancreatic lipase enzyme. The aim of this study was to build QSAR models for natural lipase inhibitors by using the Monte Carlo method. The molecular structures were represented by the simplified molecular input line entry system (SMILES) notation and molecular graphs. Three sets - training, calibration and test set of three splits - were examined and validated. Statistical quality of all the described models was very good. The best QSAR model showed the following statistical parameters: r2= 0.864 and Q2= 0.836 for the test set and r2= 0.824 and Q2= 0.819 for the validation set. Structural attributes for increasing and decreasing the activity (expressed as pIC50) were also defined. Using defined structural attributes, the design of new potential lipase inhibitors is also presented. Additionally, a molecular docking study was performed for the determination of binding modes of designed molecules.
authors.affiliation: a Department of Pharmaceutical Sciences , Guru Jambheshwar University of Science and Technology , Hisar , India.
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.affiliation: a Department of Pharmaceutical Sciences , Guru Jambheshwar University of Science and Technology , Hisar , India.
authors.forename: S
authors.initials: S
authors.lastname: Chauhan
mesh_terms: D055808:Drug Discovery / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D008049:Lipase / Q000037:antagonists & inhibitors*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009010:Monte Carlo Method; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D008049:Lipase
keywords: Monte Carlo method; Obesity; QSAR; SMILES; molecular docking; natural lipase inhibitors