Drug resistance in HIV-1 protease: Flexibility-assisted mechanism of compensatory mutations

Protein Science

Volumn 11, Issue 10, 2002, Pages 2393-2402

  Piana, Stefano ^a   Carloni, Paolo ^a,b   Rothlisberger, Ursula ^b  

^a ETH ZURICH   (Switzerland)

^b SISSA   (Italy)

Author keywords

Compensatory mutations; Drug resistance; HIV 1 protease; Molecular dynamics; Protein flexibility

Indexed keywords

MUTANT PROTEIN; PROTEINASE;

ANTIBIOTIC RESISTANCE; ARTICLE; CALCULATION; CATALYSIS; CONTROLLED STUDY; ELECTRICITY; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME CONFORMATION; ENZYME MECHANISM; ENZYME STRUCTURE; ENZYME SUBSTRATE; HUMAN IMMUNODEFICIENCY VIRUS 1; INTERMETHOD COMPARISON; MOLECULAR DYNAMICS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; QUALITATIVE ANALYSIS; SIMULATION; VIRUS MUTATION; WILD TYPE;

DRUG RESISTANCE, VIRAL; HIV PROTEASE; MUTATION; PROTEIN CONFORMATION; SUBSTRATE SPECIFICITY;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; RNA VIRUSES;

EID: 0036786493     PISSN: 09618368     EISSN: None     Source Type: Journal    
DOI: 10.1110/ps.0206702     Document Type: Article

References (59)

1. Catalytic contribution of flap-substrate hydrogen bonds in HIV-1 protease explored by chemical synthesis
2. Molecular dynamics with coupling to an external bath
3. Mapping the active site of papain with the aid of peptide substrates and inhibitors
4. The protein data bank
5. Three-dimensional structure of a mutant HIV-1 protease displaying cross-resistance to all protease inhibitors in clinical trials
6. Flap opening in HIV-1 protease simulated by 'activated' molecular dynamics
7. Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type I protease inhibitor
8. A second generation force field for the simulation of proteins, nucleic acids, and organic molecules
9. Particle mesh Ewald: An N log(N) method for Ewald sums in large systems
10. Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution
11. Structural mechanisms of HIV drug resistance
12. A smooth particle mesh Ewald method
13. Flexibility and function in HIV protease: Dynamics of the HIV-1 protease bound to the asymmetric inhibitor Kynostatin 272 (KNI-272)
14. Rapid structural fluctuations of the free HIV protease flaps in solution: Relationship to crystal structures and comparison with predictions of dynamics calculations
15. HIV protease: Enzyme function and drug resistance
16. Domain communication in the dynamical structure of human immunodeficiency virus 1 protease
17. Molecular dynamics of HIV-1 protease
18. Characterization of human immunodeficiency virus type 1 variants with increased resistance to a C2-symmetric protease inhibitor
19. Crystal structure of an in vivo HIV-1 protease mutant in complex with saquinavir: Insights into the mechanisms of drug resistance
20. 18O isotope exchange
21. Flap opening and dimer-interface flexibility in the free and inhibitor-bound HIV protease, and their implications for function
22. Synthetic peptides as substrates and inhibitors of a retroviral protease
23. Comparison of the dynamics for ground-state and transition-state structures in the active site of catechol O-Methyl transferase
24. Model free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 2. Analysis of experimental results
25. Model free approach to the interpretation of nuclear magnetic resonance relaxation in macromolecules. 1. Theory and range of validity
26. A combined quantum/classical molecular dynamics study of the catalytic mechanism of HIV protease
27. Dynamic flexibility of protein-inhibitor complexes: A study of the HIV-1 protease/KNI-272 complex
28. Structural implications of drug-resistant mutants of HIV-1 protease: High-resolution crystal structures of the mutant protease/substrate analogue complexes
29. Structural and kinetic analysis of drug resistant mutants of HIV-1 protease
30. Retracing the evolutionary pathways of human immunodeficiency virus type 1 resistance to protease inhibitors: Virus fitness in the absence and in the presence of drug
31. Selection and analysis of human immunodeficiency virus type 1 variants with increased resistance to ABT-538, a novel protease inhibitor
32. Fitness of human immunodeficiency virus type 1 protease inhibitor-selected single mutants
33. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 Å resolution
34. Flexibility and function in HIV-1 protease
35. Kinetic characterization of human immunodeficiency virus type-1 protease-resistant variants
36. Role of conformational fluctuations in the enzymatic reaction of HIV-1 protease
37. Substrate-dependent mechanism in the catalysis of human immunodeficiency virus protease
38. A cumulative specificity model for proteases form human immunodeficiency virus types 1 and 2, inferred from statistical analysis of an extended substrate data base
39. How does a symmetric dimer recognize an asymmetric substrate? A substrate complex of HIV-1 protease
40. Protein dynamics in enzymatic catalysis: Exploration of dihydrofolate reductase
41. Complete nucleotide sequence of the AIDS virus, HTLV-III
42. Drug-resistant HIV-1 protease identify enzyme residues important for substrate selection and catalytic rate
43. Three-dimensional structures of HIV-1 and SIV protease product complexes
44. Coevolution and subsite decomposition for the design of resistance-evading HIV-1 protease inhibitors
45. Predicting structural effects in HIV-1 protease mutant complexes with flexible ligand docking and protein sidechain optimization
46. Mutational anatomy of an HIV-1 protease variant conferring cross-resistance to protease inhibitors in clinical trials. Compensatory modulations of binding and activity
47. Curling of flap tips in HIV-1 protease as a mechanism for substrate entry and tolerance of drug resistance
48. The 80's loop (residues 78 to 85) is important for the differential activity of retroviral proteases
49. Rate-determining steps in HIV-1 protease catalysis
50. Calculation of the relative binding free energies of peptidic inhibitors to HIV-1 protease and its I84V mutant
51. 15N NMR relaxation measurements at two magnetic fields
52. Computational study of protein specificity: The molecular basis of HIV-1 protease drug resistance
53. Energetics of enzyme catalysis
54. Nanosecond dynamics and structure of a model DNA triple helix in salt-water solution
55. Structure-based inhibitors of HIV-1 protease
56. Inhibitors of HIV-1 protease: A major success of structure-based drug design
57. Resistance to HIV-1 inhibitors
58. Relation between sequence and structure of HIV-1 protease inhibitor complexes: A model system for the analysis of protein flexibility