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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
Bioinformatics and Biotechnology,
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