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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, Onl
J Bioinform., 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
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