©1996-2009 All Rights Reserved.
Online Journal of Bioinformatics . You may not store these pages in any form except
for your own personal use. All other usage or distribution is illegal under
international copyright treaties. Permission to use any of these pages in any
other way besides the before mentioned must be
gained in writing from the publisher. This article is exclusively copyrighted
in its entirety to OJB publications. This article may be copied once but may
not be, reproduced or re-transmitted without the
express permission of the editors. This journal satisfies the refereeing requirements
(DEST) for the Higher Education Research Data Collection (Australia). Linking:To link to this page or any
pages linking to this page you must link directly to this page only here rather
than put up your own page.
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
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.