Dynamic residue interaction network analysis of the oseltamivir binding site of N1 neuraminidase and its H274Y mutation site conferring drug resistance in influenza A virus
| Autor: | Mohini Yadav, Norifumi Yamamoto, Manabu Igarashi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Oseltamivir
Drugs and Devices Stereochemistry Biophysics medicine.disease_cause Influenza neuraminidase 01 natural sciences General Biochemistry Genetics and Molecular Biology Virus Computational Science 03 medical and health sciences Residue (chemistry) chemistry.chemical_compound Residue interaction network Interaction network 0103 physical sciences Molecular dynamics simulation Influenza A virus medicine Binding site Molecular Biology 030304 developmental biology 0303 health sciences 010304 chemical physics biology Chemistry General Neuroscience General Medicine Infectious Diseases Drug resistance Mutation (genetic algorithm) biology.protein Medicine General Agricultural and Biological Sciences Neuraminidase |
| Zdroj: | PeerJ PeerJ, Vol 9, p e11552 (2021) |
| ISSN: | 2167-8359 |
| Popis: | Background Oseltamivir (OTV)-resistant influenza virus exhibits His-to-Tyr mutation at residue 274 (H274Y) in N1 neuraminidase (NA). However, the molecular mechanisms by which the H274Y mutation in NA reduces its binding affinity to OTV have not been fully elucidated. Methods In this study, we used dynamic residue interaction network (dRIN) analysis based on molecular dynamics simulation to investigate the correlation between the OTV binding site of NA and its H274Y mutation site. Results dRIN analysis revealed that the OTV binding site and H274Y mutation site of NA interact via the three interface residues connecting them. H274Y mutation significantly enhanced the interaction between residue 274 and the three interface residues in NA, thereby significantly decreasing the interaction between OTV and its surrounding loop 150 residues. Thus, we concluded that such changes in residue interactions could reduce the binding affinity of OTV to NA, resulting in drug resistant influenza viruses. Using dRIN analysis, we succeeded in understanding the characteristic changes in residue interactions due to H274Y mutation, which can elucidate the molecular mechanism of reduction in OTV binding affinity to influenza NA. Finally, the dRIN analysis used in this study can be widely applied to various systems such as individual proteins, protein-ligand complexes, and protein-protein complexes, to characterize the dynamic aspects of the interactions. |
| Databáze: | OpenAIRE |
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