tetano
Editor, Senior Moderator
Protein Sci. 2015 Jun 5. doi: 10.1002/pro.2718. [Epub ahead of print]
[h=1]A 3D-RISM/RISM study of the oseltamivir binding efficiency with the wild-type and resistance-associated mutant forms of the viral influenza B neuraminidase.[/h] Phanich J[SUP]1[/SUP], Rungrotmongkol T[SUP]2,[/SUP][SUP]3[/SUP], Sindhikara D[SUP]4[/SUP], Phongphanphanee S[SUP]5[/SUP], Yoshida N[SUP]6[/SUP], Hirata F[SUP]7[/SUP], Kungwan N[SUP]8[/SUP], Hannongbua S[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The binding affinity of oseltamivir to the influenza B neuraminidase and to its variants with three single substitutions, E119G, R152K, and D198N, is investigated by the MM/3D-RISM method. The binding affinity or the binding free energy of ligand to receptor was found to be determined by a subtle balance of two major contributions that largely cancel out each other: the ligand-receptor interactions and the dehydration free energy. The theoretical results of the binding affinity of the drug to the mutants reproduced the observed trend in the resistivity, measured by IC[SUB]50[/SUB] ; the high-level resistance of E119G and R152K, and the low-level resistance of D198N. For E119G and R152K, reduction of the direct drug-target interaction, especially at the mutated residue, is the main source of high-level oseltamivir resistance. This phenomenon, however, is not found in the D198N strain, which is located in the framework of the active-site. This article is protected by copyright. All rights reserved.
? 2015 The Protein Society.
[h=4]KEYWORDS:[/h] 3D-RISM; Dehydration penalty; Influenza B virus; Neuraminidase; Oseltamivir resistance
PMID: 26044768 [PubMed - as supplied by publisher]
[h=1]A 3D-RISM/RISM study of the oseltamivir binding efficiency with the wild-type and resistance-associated mutant forms of the viral influenza B neuraminidase.[/h] Phanich J[SUP]1[/SUP], Rungrotmongkol T[SUP]2,[/SUP][SUP]3[/SUP], Sindhikara D[SUP]4[/SUP], Phongphanphanee S[SUP]5[/SUP], Yoshida N[SUP]6[/SUP], Hirata F[SUP]7[/SUP], Kungwan N[SUP]8[/SUP], Hannongbua S[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The binding affinity of oseltamivir to the influenza B neuraminidase and to its variants with three single substitutions, E119G, R152K, and D198N, is investigated by the MM/3D-RISM method. The binding affinity or the binding free energy of ligand to receptor was found to be determined by a subtle balance of two major contributions that largely cancel out each other: the ligand-receptor interactions and the dehydration free energy. The theoretical results of the binding affinity of the drug to the mutants reproduced the observed trend in the resistivity, measured by IC[SUB]50[/SUB] ; the high-level resistance of E119G and R152K, and the low-level resistance of D198N. For E119G and R152K, reduction of the direct drug-target interaction, especially at the mutated residue, is the main source of high-level oseltamivir resistance. This phenomenon, however, is not found in the D198N strain, which is located in the framework of the active-site. This article is protected by copyright. All rights reserved.
? 2015 The Protein Society.
[h=4]KEYWORDS:[/h] 3D-RISM; Dehydration penalty; Influenza B virus; Neuraminidase; Oseltamivir resistance
PMID: 26044768 [PubMed - as supplied by publisher]