©1996-2013
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
14 (2): 146-159, 2013
In
Silico inhibitors
for Plasmodium
falciparum lactate
dehydrogenase
Madhu Sudhana
Saddala, K. Kranthi Kumar and A. Usha Rani*
Division
of Environmental Biology, Department of Zoology, DBT
Bioinformatics Center, Sri
Venkateswara University, Tirupati A.P., India.
ABSTRACT
Madhu Sudhana
Saddala, K. Kranthi Kumar and A. Usha Rani, In Silico
Inhibitors
for Plasmodium falciparum lactate dehydrogenase, Onl
J Bioinform.,
14 (2):
146-159, 2013 Dysruption
of
receptor sites on Plasmodium
falciparum
lactate dehydrogenase (PfLDH)
could inhibit the malarial parasite. We describe Virtual
gossypol-like
compounds that might inhibit PfLDH by interacting with amino acids
on its receptors.
Multiple sequence alignment of PfLDH with Plasmodium
spp was performed with Clustal
W1.83. A phylogenetic tree was constructed with Tree Viewer
3.0. Protein structure was refined by 2ns
molecular
simulation and energy minimization.
Compounds (1997) were then screened Virtually
(Autodoc Vina)
for similarity with
gossypol from The Zinc database for binding capacity. Docking
showed that
sequentially ZINC27313038,
ZINC13759138,
ZINC13759183,
ZINC13759202,
ZINC59648667 and
ZINC11159075
k.cal/mol
had most binding
capacity with PfLDH
compared with gossipol. These compounds
bind by hydrogen
bonds and hydrophobic interactions and may
inhibit PfLDH
mediated glycolysis The
cavity surrounded
by Ile31, Gly99, Asn140, Gly32, Thr101, Gly29 Thr97, Asp53,
Met30, Phe52 and
Glu122 may possibly be manipulated to inhibit the parasite.
Keywords: PfLDH,
NAMD, MDSimulation,
Virtual screening, Docking, Zinc database