HIV Mutation Detail Information

Virus Mutation HIV Mutation I47V


Basic Characteristics of Mutations
Mutation Site I47V
Mutation Site Sentence To elucidate the binding mechanism of HIV-1 protease with promising inhibitor GRL-02031 and further to probe the resistance mechanism associated with mutations (I47V, L76V, V82A, and N88D) to the inhibitor, we applied multiple molecular dynamics (MMD) simulations along with energy analysis by the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and solvated interaction energy (SIE) methodology on specific HIV-1 protease with GRL-0231 complexes.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region PR
Standardized Encoding Gene gag-pol  
Genotype/Subtype HIV-1
Viral Reference -
Functional Impact and Mechanisms
Disease HIV Infections    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 33175558
Title Multiple Molecular Dynamics Simulations of the Inhibitor GRL-02031 Complex with Wild Type and Mutant HIV-1 Protease Reveal the Binding and Drug-Resistance Mechanism
Author Wang R,Zheng Q
Journal Langmuir : the ACS journal of surfaces and colloids
Journal Info 2020 Nov 24;36(46):13817-13832
Abstract Human immunodeficiency virus type 1 (HIV-1) protease is regarded as a fascinating target for drug development against HIV infection. However, mutations causing drug resistance severely limit the efficiency of the recently marketed drugs in the treatment of HIV replication. To elucidate the binding mechanism of HIV-1 protease with promising inhibitor GRL-02031 and further to probe the resistance mechanism associated with mutations (I47V, L76V, V82A, and N88D) to the inhibitor, we applied multiple molecular dynamics (MMD) simulations along with energy analysis by the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and solvated interaction energy (SIE) methodology on specific HIV-1 protease with GRL-0231 complexes. On the basis of detail analysis of the simulations, we revealed key characteristics that constitute the drug resistance of four mutation HIV-1 proteases toward GRL-02031: substitution of the side chain in these four mutation residues leads to a change in the distances between the flaps and catalytic sites, thereby reducing the affinity for GRL-02031 with these four mutation proteases, even though the L76V and N88D residues cannot directly contact GRL-02031. The results of energy analysis according to the MM-PBSA and SIE methods further indicated that hydrophobic interaction was considered to be the prime driving force for inhibitor GRL-02031 binding to protease and the decrease in van der Waals interactions between inhibitor GRL-02031 and mutant proteases as the primary cause of the drug resistance. Analyses of the hydrogen bonds and atomic interactions further provided detailed explanations for the resistance of these four mutation proteases toward inhibitor GRL-02031. The present study provides potential guidance on the structure-based inhibitors' design targeting HIV-1 protease.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.