Back to Search
Start Over
Computational investigation of drug-resistant mutant of M2 proton channel (S31N) against rimantadine.
- Source :
-
Cell biochemistry and biophysics [Cell Biochem Biophys] 2014 Nov; Vol. 70 (2), pp. 975-82. - Publication Year :
- 2014
-
Abstract
- M2 proton channel is the target for treating the patients who ere suffering from influenza A infection, which facilitates the spread of virions. Amantadine and rimantadine are adamantadine-based drugs, which target M2 proton channel and inhibit the viral replication. Preferably, rimantadine drug is used more than amantadine because of its fewer side effects. However, S31N mutation in the M2 proton channel was highly resistant to the rimantadine drug. Therefore, in the present study, we focused to understand the drug-resistance mechanism of S31N mutation with the aid of molecular docking and dynamics approach. The docking analysis undoubtedly indicates that affinity for rimantadine with mutant-type M2 proton channel is significantly lesser than the native-type M2 proton channel. In addition, RMSD, RMSF, and principal component analysis suggested that the mutation shows increased flexibility. Furthermore, the intermolecular hydrogen bonds analysis showed that there is a complete loss of hydrogen bonds in the mutant complex. On the whole, we conclude that the intermolecular contact was maintained by D-44, a key residue for stable binding of rimantadine. These findings are certainly helpful for better understanding of drug-resistance mechanism and also helpful for designing new drugs for treating influenza infection against drug-resistance target.
- Subjects :
- Antiviral Agents metabolism
Antiviral Agents pharmacology
Crystallography, X-Ray
Protein Conformation
Protein Stability
Proton Pumps chemistry
Proton Pumps metabolism
Drug Resistance, Viral genetics
Molecular Docking Simulation
Molecular Dynamics Simulation
Mutation
Proton Pumps genetics
Rimantadine metabolism
Rimantadine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0283
- Volume :
- 70
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 24807842
- Full Text :
- https://doi.org/10.1007/s12013-014-0005-6