Publication: Key interactions of the mutant HIV-1 reverse transcriptase/efavirenz: An evidence obtained from ONIOM method
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Issued Date
2011
Resource Type
File Type
application/pdf
ISSN
20402503
Other identifier(s)
2-s2.0-82455186221
Rights Holder(s)
Scopus
Bibliographic Citation
MedChemComm. Vol 2, No.12 (2011), p.1181-1187
Suggested Citation
Boonsri P., Kuno M., Hannongbua S. Key interactions of the mutant HIV-1 reverse transcriptase/efavirenz: An evidence obtained from ONIOM method. MedChemComm. Vol 2, No.12 (2011), p.1181-1187. doi:10.1039/c1md00162k Retrieved from: https://hdl.handle.net/20.500.14740/7214
Author(s)
Abstract
Two-layered ONIOM calculations were performed in order to compare the binding of efavirenz (EFV) to the HIV-1 RT binding pocket of both wild type (WT) and K103N enzymes. The K103N mutation reduces the binding affinity of the inhibitor by 5.81 kcal mol -1 as obtained from the ONIOM2 (B3LYP/6-31G(d,p):PM3) method. These indicate that the loss of binding energy to K103N mutation can attribute to a weakened attractive interaction between the drug and residues surrounding in the binding pocket. The deformation of the K103N binding pocket requires more energy for structural rearrangement than that of the WT by approximately 4.0 kcal mol -1. Moreover, the pairwise energies perfectly demonstrate that the K103N mutation affects on the loss of the interaction energy. In addition, the main influences are due to residues surrounding in the binding pocket; K101, K102, S105, V179, W229, P236 and E138. In particular, two residues; K101 and S105, established hydrogen bondings with the inhibitor. ONIOM calculations, resulting in the details of binding energy, interaction energy and deformation energy can be used to identify the key interaction and structural requirements of more potent HIV-1 RT inhibitor. © 2011 The Royal Society of Chemistry.