literature

Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease.

PMID: 19629548 2010 Journal of molecular modeling

Abstract: Detailed binding free energies between TMC-114 and individual protein residues are computed by using a per-residue basis decomposition method, which provides insights into the inhibitor-protein binding mechanism and also explains the drug-resistant mechanisms of mutations D30N and I50V to TMC-114.

Abstract: In this work, molecular dynamics (MD) simulations combined with the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method have been performed to investigate the drug-resistant mechanisms of D30N and I50V to an inhibitor TMC-114.

Abstract: The analyses of absolute binding free energies using the separate trajectory approach suggests that the decrease in the van der Waals energy and electrostatic energy in the gas phase results in the drug resistance of D30N to TMC-114, while for

PMID: 20055526 2010 The journal of physical chemistry. B

Abstract: The effect of the V82I mutation on the association with chemicals and the reason for rare appearance of the D30N mutation in subtype C HIV-1 were discussed in terms of the change of geometry of the residues in HIV-1 protease.

Effect of human immunodeficiency virus type 1 protease inhibitor therapy and subtype on development of resistance in subtypes B and G.

PMID: 19577015 2010 Infection, genetics and evolution

Abstract: We confirmed previous reports on the subtype-dependent selection of D30N and 89I, and identified a new mutation with such differential selective pressure: 37D was preferentially selected by lopinavir in subtype B.

HIV drug resistance surveillance using pooled pyrosequencing.

PMID: 20174661 2010 PloS one

Table: D30N

Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells.

PMID: 21124822 2010 PLoS pathogens

Method: The PR mutants, L10I, K20R, D25G, T26S, D30N, I54V, L63P, V82A and L90M were created on the pEYFP-C1PR plasmid with the Quick-Exchange Site-directed Mutagenesis Kit (Stratagene, La Jolla, CA).

Result: By contrast, D30N, F53L, and L90M all produced Casp8p41:gag-pol cleavage ratios greater than WT protease (Figure 8B).

Result: For this we chose the DAMs I54V,

PMID: 21603285 2010 The open medical informatics journal

Abstract: Using a bioinformatics-based model to assess the effects of numerous drug resistance mutations, we determined that the D30N mutation in HIV-1 protease had the largest decrease in replication capacity among known protease resistance mutations.

Abstract: We found HIV-1 containing the D30N mutation had a significant defect in vivo, showing impaired replication kinetics and a decreased ability to deplete CD4+ thymocytes, compared to the wild-type or virus without the D30N mutation.

Introduction: The D30N has been identified to biochemically alter viral proteas

Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease.

PMID: 20541446 2010 Journal of molecular graphics & modelling

Abstract: D30N appears to facilitate conformational changes in subtype B PR, but not in that from subtype C, and this could be associated with disestablishment of an alpha-helical region of the PR.

Abstract: Among patients who do not respond to treatment with the PI nelfinavir (NFV), the D30N mutation is often observed.

Abstract: However, several reports have shown that D30N emerges with different frequencies in distinct HIV-1 genetic forms or subtypes.

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: 20660190 2010 Journal of virology

Abstract: AE protease has been observed to develop resistance through a nonactive-site N88S mutation in response to nelfinavir (NFV) therapy, whereas clade B protease develops both the active-site mutation D30N and the nonactive-site mutation N88D.

Abstract: The D30N/N88D mutations in clade B resulted in a significant loss of affinity for NFV and, to a lesser extent, for DRV.

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.

Abstract: When all the mutants were ranked in order from most to least fit for both assays, 4 protease mutants moved more than 5 positions in rank: the D30N, I54L, I54M, and V82A mutants.