Publication: Insights into saquinavir resistance in the G48V HIV-1 protease: Quantum calculations and molecular dynamic simulations
Issued Date
2005-01-01
Resource Type
ISSN
00063495
Other identifier(s)
2-s2.0-18344371990
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biophysical Journal. Vol.88, No.2 (2005), 867-879
Suggested Citation
Kitiyaporn Wittayanarakul, Ornjira Aruksakunwong, Suwipa Saen-Oon, Wasun Chantratita, Vudhichai Parasuk, Pornthep Sompornpisut, Supot Hannongbua Insights into saquinavir resistance in the G48V HIV-1 protease: Quantum calculations and molecular dynamic simulations. Biophysical Journal. Vol.88, No.2 (2005), 867-879. doi:10.1529/biophysj.104.046110 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/16397
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Insights into saquinavir resistance in the G48V HIV-1 protease: Quantum calculations and molecular dynamic simulations
Other Contributor(s)
Abstract
The spread of acquired immune deficiency syndrome has increasingly become a great concern owing largely to the failure of chemotherapies. The G48V is considered the key signature residue mutation of HIV-1 protease developing with saquinavir therapy. Molecular dynamics simulations of the wild-type and the G48V HIV-1 protease complexed with saquinavir were carried out to explore structure and interactions of the drug resistance. The molecular dynamics results combined with the quantum-based and molecular mechanics Poisson-Boltzmann surface area calculations indicated a monoprotonation took place on D25, one of the triad active site residues. The inhibitor binding of the triad residues and its interaction energy in the mutant were similar to those in the wild-type. The overall structure of both complexes is almost identical. However, the steric conflict of the substituted valine results in the conformational change of the P2 subsite and the disruption of hydrogen bonding between the -NH of the P2 subsite and the backbone -CO of the mutated residue. The magnitude of interaction energy changes was comparable to the experimental Ki data. The designing for a new drug should consider a reduction of steric repulsion on P2 to enhance the activity toward this mutant strain. © 2005 by the Biophysical Society.