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Computational Study of Drug Binding Affinity to Influenza A Neuraminidase Using Smooth Reaction Path Generation (SRPG) Method.
Computational Study of Drug Binding Affinity to Influenza A Neuraminidase Using Smooth Reaction Path Generation (SRPG) Method.
- Source :
-
Journal of chemical information and modeling [J Chem Inf Model] 2015 Sep 28; Vol. 55 (9), pp. 1936-43. Date of Electronic Publication: 2015 Sep 08. - Publication Year :
- 2015
-
Abstract
- Assessment of accurate drug binding affinity to a protein remains a challenge for in silico drug development. In this research, we used the smooth reaction path generation (SRPG) method to calculate binding free energies and determine potential of mean forces (PMFs) along the smoothed dissociation paths of influenza A neuraminidase and its variants with oseltamivir (Tamiflu) and zanamivir (Relenza) inhibitors. With the gained results, we found that the binding free energies of neuraminidase A/H5N1 in WT and two mutants (including H274Y and N294S) with oseltamivir and zanamivir show good agreement with experimental results. Additionally, the thermodynamic origin of the drug resistance of the mutants was also discussed from the PMF profiles.
- Subjects :
- Catalytic Domain
Drug Delivery Systems
Drug Resistance
Forecasting
Humans
Influenza A Virus, H5N1 Subtype metabolism
Ligands
Models, Biological
Oseltamivir chemistry
Protein Binding
Thermodynamics
Zanamivir chemistry
Computer Simulation
Influenza A Virus, H5N1 Subtype enzymology
Neuraminidase chemistry
Neuraminidase metabolism
Oseltamivir metabolism
Zanamivir metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1549-960X
- Volume :
- 55
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of chemical information and modeling
- Publication Type :
- Academic Journal
- Accession number :
- 26247106
- Full Text :
- https://doi.org/10.1021/acs.jcim.5b00319