title: Computational Study of Drug Binding Affinity to Influenza A Neuraminidase Using Smooth Reaction Path Generation (SRPG) Method.
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.
authors.affiliation: Life Science Laboratory, Institute for Computational Science and Technology , Ho Chi Minh City, Vietnam.
authors.forename: Hung
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: University of Technology , Ho Chi Minh City, Vietnam.
authors.forename: Tien
authors.initials: T
authors.lastname: Tran
authors.affiliation: National Institute of Advanced Industrial Science and Technology , Tokyo, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Fukunishi
authors.affiliation: Institute for Protein Research, Osaka University , Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Higo
authors.affiliation: Institute for Protein Research, Osaka University , Osaka, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Life Science Laboratory, Institute for Computational Science and Technology , Ho Chi Minh City, Vietnam.|School of Biotechnology, International University, Vietnam National University , Ho Chi Minh City, Vietnam.
authors.forename: Ly
authors.initials: L
authors.lastname: Le
mesh_terms: D020134:Catalytic Domain; D003198:Computer Simulation; D016503:Drug Delivery Systems; D004351:Drug Resistance; D005544:Forecasting; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology* / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D009439:Neuraminidase / Q000737:chemistry* / Q000378:metabolism*; D053139:Oseltamivir / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013816:Thermodynamics; D053243:Zanamivir / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir