©1996-2019 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.
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,
of 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, 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