A Study of the Binding Energies of Efavirenz to Wild-Type and K103N/Y181C HIV-1 Reverse Transcriptase Based on the ONIOM Method

✍ Scribed by Pensri Srivab; Supa Hannongbua

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 697 KB
• Volume: 3
• Category: Article
• ISSN: 1860-7179
• DOI: 10.1002/cmdc.200700181

✦ Synopsis

Abstract

A three‐layered ONIOM model was used to study the interactions between efavirenz and the binding sites of HIV‐1 reverse transcriptase (RT): wild‐type and double mutant K103N/Y181C enzyme forms. Binding energies were determined and compared to describe the loss of activity of efavirenz with the mutant HIV‐1 RT binding pocket. The calculated binding energy for the efavirenz–K103N/Y181C HIV‐1 RT complex is less than that with the wild‐type complex by approximately 8 kcal mol^−1^. The interaction energies, calculated at the MP2/6‐31G(d,p) level between efavirenz and individual residues surrounding the binding pocket of the K103N/Y181C enzyme, demonstrate that the attractive interactions between efavirenz and residue positions 101 and 103 were less than those for wild‐type RT by 5.52 and 3.62 kcal mol^−1^, respectively. Understanding these interactions could be useful in the design of inhibitors specific for the HIV‐1 RT allosteric site and that have greater potency against the mutant enzyme.