EBOV Mutation Detail Information

Virus Mutation EBOV Mutation K251A


Basic Characteristics of Mutations
Mutation Site K251A
Mutation Site Sentence Moreover, the binding free energy calculations show that I295A and K248A/I295A mutations decrease of absolute binding free energies while K248A and K251A mutations increase absolute binding free energy.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region VP35
Standardized Encoding Gene VP35
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 26466951
Title Exploring interaction mechanisms of the inhibitor binding to the VP35 IID region of Ebola virus by all atom molecular dynamics simulation method
Author Zhang YJ,Ding JN,Feng TT,Han JG
Journal Proteins
Journal Info 2015 Dec;83(12):2263-78
Abstract Ebola viruses (EBOVs) cause an acute and serious illness which is often fatal if untreated, and there is no effective vaccine until now. Multifunctional VP35 is critical for viral replication, RNA silencing suppression and nucleocapsid formation, and it is considered as a future target for the molecular biology technique. In the present work, the binding of inhibitor pyrrole-based compounds (GA017) to wild-type (WT), single (K248A, K251A, and I295A), and double (K248A/I295A) mutant VP35 were investigated by all-atom molecular dynamic (MD) simulations and Molecular Mechanics Generalized Born surface area (MM/GBSA) energy calculation. The calculated results indicate that the binding with GA017 makes the binding pocket more stable and reduces the space of the binding pocket. Moreover, the electrostatic interactions (DeltaEele) and VDW energy (DeltaEvdw) provide the major forces for affinity binding, and single mutation I295A and double mutation K248A/I295A have great influence on the conformation of the VP35 binding pocket. Interestingly, the residues R300-G301-D302 of I295A form a new helix and the sheet formed by the residues V294-I295-H296-I297 disappears in the double mutation K248A/I295A as compared with WT. Moreover, the binding free energy calculations show that I295A and K248A/I295A mutations decrease of absolute binding free energies while K248A and K251A mutations increase absolute binding free energy. Our calculated results are in good agreement with the experimental results that K248A/I295A double mutant results in near-complete loss of compound binding. The obtained information will be useful for design effective inhibitors for treating Ebola virus.
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.