A NEW TARGET FOR DIABETES: HOMOLOGY MODELING AND IDENTIFICATION OF POTENTIAL LEADS THROUGH VIRTUAL SCREENINGAbstract
Monocarboxylate transporter 11 (MCT11) is a transporter protein encoded by the SLC16A11 gene. MCT11 protein is found to play an important role in many biological activities in different species. MCT11 helps in hepatic lipid metabolism by catalyzing the transport of pyruvate molecules across the membrane. It is also found to be involved in regulation of Diabetes. Therefore, MCT11 protein is taken into consideration for this study. Moreover, a rapid analysis through different protein databases revealed that there is no protein crystal structure available. Therefore, Homology modeling is adopted to generate the model using SWISS-MODEL and validated using PROCHECK. More specifically, this is the first Homology model developed for the MCT11 protein. The sequence analysis studies such as physicochemical properties such as molecular weight (47790.99 Da), Theoretical isoelectric point (8.67), Total number of positively (Asp+Glu) and negatively (Arg+Lys) charged residues (+R/-R) were 19 and 22 respectively. The grand average of hydropathicity (GRAVY) indicating a value of 0.687 was computed. The secondary structure prediction and conserved domain sequence were computed. Finally, the modeled protein subjected to virtual screening to identify the possible leads using PyRX software, which uses the Autodock Vina module for virtual screening. About 1943 compounds were screened virtually and 10 compounds were found to be extremely effective having binding energies range from -11.0 Kcal/mol to -11.60 Kcal/mol.
K. N. Kumar *, N. V. Sreedevi and P. Spandana
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Medicinal Chemistry, Hyderabad, Telangana, India.
16 March 2019
12 June 2019
16 November 2019
01 December 2019