NDLI: Role of R292K mutation in influenza H7N9 neuraminidase toward oseltamivir susceptibility: MD and MM/PB(GB)SA study

Content Provider	Springer Nature Link
Author	Phanich, Jiraphorn Rungrotmongkol, Thanyada Kungwan, Nawee Hanngbua, Supot
Copyright Year	2016
Abstract	The H7N9 avian influenza virus is a novel re-assortment from at least four different strains of virus. Neuraminidase, which is a glycoprotein on the surface membrane, has been the target for drug treatment. However, some H7N9 strains that have been isolated from patient after drug treatment have a R292K mutation in neuraminidase. This substitution was found to facilitate drug resistance using protein- and virus- assays, in particular it gave a high resistance to the most commonly used drug, oseltamivir. The aim of this research is to understand the source of oseltamivir resistance using MD simulations and the MM/PB(GB)SA binding free energy approaches. Both methods can predict the reduced susceptibility of oseltamivir in good agreement to the IC $_{ 50 }$ binding energy, although MM/GBSA underestimates this prediction compared to the MM/PBSA calculation. Electrostatic interaction is the main contribution for oseltamivir binding in terms of both interaction and solvation. We found that the source of the drug resistance is a decrease in the binding interaction combined with the reduction of the dehydration penalty. The smaller K292 mutated residue has a larger binding pocket cavity compared to the wild-type resulting in the loss of drug carboxylate-K292 hydrogen bonding and an increased accessibility for water molecules around the K292 mutated residue. In addition, oseltamivir does not bind well to the R292K mutant complex as shown by the high degree of fluctuation in ligand RMSD during the simulation and the change in angular distribution of bulky side chain groups.
Starting Page	917
Ending Page	926
Page Count	10
File Format	PDF
ISSN	0920654X
Journal	Journal of Computer-Aided Molecular Design
Volume Number	30
Issue Number	10
e-ISSN	15734951
Language	English
Publisher	Springer International Publishing
Publisher Date	2016-10-06
Publisher Place	Cham
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	H7N9 influenza neuraminidase R292K mutant Molecular dynamics simulation MM/PB(GB)SA Physical Chemistry Computer Applications in Chemistry Animal Anatomy / Morphology / Histology
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Physical and Theoretical Chemistry Computer Science Applications

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Discover binding pathways using the sliding binding-box docking approach: application to binding pathways of oseltamivir to avian influenza H5N1 neuraminidase

Structural Investigations and Binding Mechanisms of Oseltamivir Drug Resistance Conferred by the E119V Mutation in Influenza H7N9 Virus

Sensitivity of molecular docking to induced fit effects in influenza virus neuraminidase

QSAR analyses on avian influenza virus neuraminidase inhibitors using CoMFA, CoMSIA, and HQSAR

Mixed QM/MM molecular electrostatic potentials

Theoretical insights into the molecular mechanism of I117V mutation in neuraminidase mediated reduction of oseltamivir drug susceptibility in A/H5N1 influenza virus

MM/GBSA and LIE estimates of host–guest affinities: dependence on charges and solvation model

Characterization of PDZ domain–peptide interactions using an integrated protocol of QM/MM, PB/SA, and CFEA analyses

Theoretical descriptors for the quantitative rationalisation of plastocyanin mutant functional propertiess

Role of R292K mutation in influenza H7N9 neuraminidase toward oseltamivir susceptibility: MD and MM/PB(GB)SA study

Similar Documents

Discover binding pathways using the sliding binding-box docking approach: application to binding pathways of oseltamivir to avian influenza H5N1 neuraminidase

Structural Investigations and Binding Mechanisms of Oseltamivir Drug Resistance Conferred by the E119V Mutation in Influenza H7N9 Virus

Sensitivity of molecular docking to induced fit effects in influenza virus neuraminidase

QSAR analyses on avian influenza virus neuraminidase inhibitors using CoMFA, CoMSIA, and HQSAR

Mixed QM/MM molecular electrostatic potentials

Theoretical insights into the molecular mechanism of I117V mutation in neuraminidase mediated reduction of oseltamivir drug susceptibility in A/H5N1 influenza virus

MM/GBSA and LIE estimates of host–guest affinities: dependence on charges and solvation model

Characterization of PDZ domain–peptide interactions using an integrated protocol of QM/MM, PB/SA, and CFEA analyses

Theoretical descriptors for the quantitative rationalisation of plastocyanin mutant functional propertiess

Role of R292K mutation in influenza H7N9 neuraminidase toward oseltamivir susceptibility: MD and MM/PB(GB)SA study