Decomposing the energetic impact of drug resistant mutations in HIV-1 protease on binding DRV.
PMID: 20543885
2010
Journal of chemical theory and computation
Abstract: Two drug-resistant protease variants FLAP+ (L10I, G48V, I54V, V82A) and ACT (V82T, I84V) decrease the binding affinity with DRV by 1.0 kcal/mol and 1.6 kcal/mol respectively.
Introduction: In this study, the binding of DRV was investigated with wild-type HIV-1 protease and two drug-resistant variants: FLAP+ (Figure 1B) with L10I, G48V, I54V, V82A which are a combination of flap and active site mutations, and ACT (Figure 1C) with V82T, I84V which are active site mutations.
Discussion: In this st
Comparison of protease inhibitor (PI) resistance-associated mutations between PI-naive and PI-experienced HIV-1 infected patients in Thailand where subtype A/E is predominant.
Abstract: The most common primary PI-RAMs in the latter group were V82A (10%), I54V (7%) and G48V (4.8%).
HIV-1 protease mutations and protease inhibitor cross-resistance.
PMID: 20660676
2010
Antimicrobial agents and chemotherapy
Abstract: Of the mutations with the greatest effect on PI susceptibility, I84AV was associated with decreased susceptibility to eight PIs; V32I, G48V, I54ALMSTV, V82F, and L90M were associated with decreased susceptibility to six to seven PIs; I47A, G48M, I50V, L76V, V82ST, and N88S were associated with decreased susceptibility to four to five PIs; and D30N, PMID: 20695887
2010
The FEBS journal
Discussion: Also, the structure of PRG48V-DRV showed reduced volume of the active site cavity relative to the wild type complex, consistent with a major effect of the G48V rather than the L90M mutation in reducing the S1/S1' volume in PRG48V/L90M-SQV.
Human immunodeficiency virus type 1 protease inhibitor drug-resistant mutants give discordant results when compared in single-cycle and multiple-cycle fitness assays.
PMID: 20826651
2010
Journal of clinical microbiology
Abstract: Five protease mutants showed statistically different fitness values by the MCA versus the SCA: the D30N, G48V, I50V, I54L, and I54M mutants.
Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure.
PMID: 18992847
2009
Infection, genetics and evolution
Method: Mutations D30N (NFV), V32I (LPV), M46I/L (IDV/RTV), I47V/A (LPV/RTV), G48V (SQV), I50L/V (APV), V82A/F/T/S (LPV/IDV/RTV), I84V (APV/IDV/RTV) and L90M (SQV/NFV) were considered as major resistance mutations and were analyzed separately for each PI as well as quantitatively all together.
Table: G48V
Proteochemometric modeling of drug resistance over the mutational space for multiple HIV protease variants and multiple protease inhibitors.
PMID: 19391634
2009
Journal of chemical information and modeling
Abstract: The model revealed the most deleterious mutations in the protease to be D30N, V32I, G48V, I50V, I54V, V82A, I84V, and L90M.
Role of atazanavir in the treatment of HIV infection.
PMID: 19436623
2009
Therapeutics and clinical risk management
Introduction: Mutations more significant to be included in the GIQ model are the following: L10F/I/V, K20M/R, L24I, D30N, V32I, L33F, M36I/L, I47V/A, G48V, I50V, I50L, F53L, I54V/L/A/M/T/S, L63P, A71V/T, G73S, V77I, V82A/F/T, I84V, N88D/S and
Rapid and accurate prediction of binding free energies for saquinavir-bound HIV-1 proteases.
PMID: 18225901
2008
Journal of the American Chemical Society
Abstract: A detailed analysis of the enthalpic/entropic balance of drug-protease interactions explains resistance in L90M in terms of a higher vibrational entropy than in the WT complex, while G48V disrupts critical hydrogen bonds at the inhibitor's binding site and produces an altered, more unfavorable balance of Coulomb and polar desolvation energies.
Abstract: Herein we report an application of the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) technique to the ranking of binding affinities of the inhibitor saquinavir with the wild type (WT) and three resistant mutants of HIV-1 protease: L90M, G48V, and G48V/L90M.
Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavir.
Abstract: PR(G48V) was about twofold less susceptible to SQV than to DRV, whereas the opposite was observed for PR(I50V).
Abstract: The crystal structures of flap mutants PR(I50V) (PR with I50V mutation), PR(I54V) (PR with I54V mutation), and PR(I54M) (PR with I54M mutation) complexed with saquinavir (SQV) as well as PR(G48V) (PR with
HIV mutation literature information.
PMID: 
2010
Journal of chemical theory and computation
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