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OJBTM
Online Journal of Bioinformatics©

  

Volume 10 (1): 1-13, 2009.


Homology modelling, molecular dynamics and docking studies of human GLUT5 protein involved in intestinal transport.

 

Padmavathi GV1,  Nataraj Sekhar P2, Saralakumari D1 

 

 

1Department of Biochemistry, Sri Krishnadevaraya University, Anantapur.2 Katholike University (Leuven), Belgium

 

 

ABSTRACT

 

Padmavathi GV,  Nataraj Sekhar P, Saralakumari D., Homology modelling, molecular dynamics and docking studies of human GLUT5 protein involved in Intestinal transport, Online J Bioinformatics 10(1):1-13, 2009. GLUT 5 is a high-affinity fructose transporter, with an apparently poor ability to transport glucose. It is distributed in the intestine, testis, kidney, skeletal muscle, fat tissue and brain and is significantly involved in diabetes, hypertension, obesity, inflammation and overian cancer. To predict the structure of GLUT5 protein and to understand the mechanisms of sweeteners and inhibitors interaction, a three-dimensional model was generated based on the crystal structure of Glutaminase Domain of Glucosamine 6-Phosphate Synthase (PDB: 1XFF) by using MODELLER7v7. The structure having a least modeller objective function was used as a starting point for picoseconds‑duration molecular dynamics simulations. With the aid of the molecular dynamics and minimization methods, the final refined model was obtained and was further assessed by ERRAT, WHATCHECK and PROCHECK, which suggested that the refined model was reliable. Docking studies were performed using this model with sweeteners and inhibitors.  The results indicate that the saccharide fructose has more affinity than the other sweeteners. Among the studied competitively interacting molecules ingliforib showed more interaction with GLUT5. The docking studies also suggest that Asn 94, Lys156, Asn 157 and Gln 178 are important determinant residues in binding with ligands, as they are highly involved in hydrogen bond interactions with the ligands.

 

Key words: GLUT5, homology modelling, Molecular Dynamics, Docking.


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