Abstract
The effect of the K103N mutation of HIV-1 reverse transcriptase (RT) on the activity of efavirenz analogues was studied via Monte Carlo/free energy perturbation calculations. The relative fold resistance energies indicate that efavirenz binds to K103N RT in a manner similar to the wild-type enzyme. The improved performance of the quinazolinones against the mutant enzyme is attributed to formation of a more optimal hydrogen-bonding network with bridging water molecules between the ligands and Glu138.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Alkynes
-
Benzoxazines
-
Cyclopropanes
-
HIV Reverse Transcriptase / chemistry*
-
HIV Reverse Transcriptase / genetics*
-
Models, Molecular
-
Monte Carlo Method
-
Mutation
-
Oxazines / chemistry*
-
Protein Binding
-
Reverse Transcriptase Inhibitors / chemistry*
-
Thermodynamics
Substances
-
Alkynes
-
Benzoxazines
-
Cyclopropanes
-
Oxazines
-
Reverse Transcriptase Inhibitors
-
HIV Reverse Transcriptase
-
efavirenz
Associated data
-
PDB/1FKO
-
PDB/1IKV
-
PDB/1RT3
-
PDB/1RTI