title: In silico modelling and molecular dynamics simulation studies of thiazolidine based PTP1B inhibitors.
abstract: Protein tyrosine phosphatase 1B (PTP1B) has been identified as a negative regulator of insulin and leptin signalling pathway; hence, it can be considered as a new therapeutic target of intervention for the treatment of type 2 diabetes. Inhibition of this molecular target takes care of both diabetes and obesity, i.e. diabestiy. In order to get more information on identification and optimization of lead, pharmacophore modelling, atom-based 3D QSAR, docking and molecular dynamics studies were carried out on a set of ligands containing thiazolidine scaffold. A six-point pharmacophore model consisting of three hydrogen bond acceptor (A), one negative ionic (N) and two aromatic rings (R) with discrete geometries as pharmacophoric features were developed for a predictive 3D QSAR model. The probable binding conformation of the ligands within the active site was studied through molecular docking. The molecular interactions and the structural features responsible for PTP1B inhibition and selectivity were further supplemented by molecular dynamics simulation study for a time scale of 30 ns. The present investigation has identified some of the indispensible structural features of thiazolidine analogues which can further be explored to optimize PTP1B inhibitors.
authors.affiliation: a University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India.
authors.forename: Manoj Kumar
authors.identifier: http://orcid.org/0000-0001-8147-5283
authors.initials: MK
authors.lastname: Mahapatra
authors.affiliation: b Department of Bioinformatics , Centre for Biological Sciences, Central University of South Bihar , BIT campus, Patna , India.
authors.forename: Krishnendu
authors.identifier: http://orcid.org/0000-0001-9966-5907
authors.initials: K
authors.lastname: Bera
authors.affiliation: b Department of Bioinformatics , Centre for Biological Sciences, Central University of South Bihar , BIT campus, Patna , India.
authors.forename: Durg Vijay
authors.initials: DV
authors.lastname: Singh
authors.affiliation: a University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India.
authors.forename: Rajnish
authors.initials: R
authors.lastname: Kumar
authors.affiliation: a University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D055808:Drug Discovery; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D053778:Thiazolidines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D053778:Thiazolidines; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: 3D QSAR; PTP1B; docking; molecular dynamics; thiazolidine