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OJBTM
Online Journal of Bioinformatics©
Volume 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 J Bioinformatics, 8(1):99-114, 2007. 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