©1996-2007
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©
8 (1) : 99-114, 2007
Binding
Modes, binding Affinities and ADME
Screening of HIV-1 NNRTI Inhibitor: Efavirnez
and its
analogues.
Sengupta D, Verma D,
Department
of Bioinformatics and Biotechnology,
ABSTRACT
Sengupta D, Verma
D, Naik PK Binding
Modes, Binding Affinities and ADME
Screening of HIV-1 NNRTI Inhibitor: Efavirnez
and its
analogues, Online
Journal of Bioinformatics, 8(1):99-114, Synthetic
analogues of Efavirnez have been used to
create efficient
safer anti-HIV drugs. Forty seven analogues using combinatorial design
with structural
modifications at X, Y and R of the parent Efavirnez
structure
are herein described. Molecular interactions and binding affinities
with Reverse
Transcriptase 1 (RT) using docking-MM-GB/SA screening based on ADME
properties are
illustrated. Results showed that these analogues docked in a similar
position
and orientation on the active site of RT. A linear correlation (r2
=
0.9948) was observed between the calculated free energy of binding
(FEB) and pIC50
for the inhibitors, suggesting that the docked structure orientation
and
interaction energies were accurate. Three H-bonds between Efavirnez
analogues and RT were observed. The electrostatic energy estimated by
GB/SA predicted
binding affinity (R2 = 17.2 %). However, few Efavirnez
analogues showed high binding affinity and activity with RT compared
with the co-crystallized
compound. This work describes modifications to the
X, Y and R substitutes in Efavirenz.
Key words: Reverse
transcriptase, Efavirnez,
Docking, Glide, FEB, pIC50, ADME