Document Detail

Evaluating how rimantadines control the proton gating of the influenza A M2-proton port via allosteric binding outside of the M2-channel: MD simulations.
MedLine Citation:
PMID:  20583869     Owner:  NLM     Status:  In-Data-Review    
In order to understand how rimantadine (RMT) inhibits the proton conductance in the influenza A M2 channel via the recently proposed "allosteric mechanism", molecular dynamics simulations were applied to the M2-tetrameric protein with four RMTs bound outside the channel at the three protonation states: the 0H-closed, 1H-intermediate and 3H-open situations. In the 0H-closed state, a narrow channel with the RMT-Asp44-Trp41 H-bond network was formed, therefore the water penetration through the channel was completely blocked. The Trp41-Asp44 interaction was absent in the 1H-intermediate state, whilst the binding of RMT to Asp44 remained, which resulted in a weakened helix-helix packing, therefore the channel was partially prevented. In the 3H-open state it was found that the electrostatic repulsion from the three charged His37 residues allowed the Trp41 gate to open, permitting water to penetrate through the channel. This agreed well with the potential of the means force which is in the following order: 0H > 1H > 3H.
Pathumwadee Intharathep; Thanyada Rungrotmongkol; Panita Decha; Nadtanet Nunthaboot; Nopphorn Kaiyawet; Teerakiat Kerdcharoen; Pornthep Sompornpisut; Supot Hannongbua
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Publication Detail:
Type:  Journal Article     Date:  2010-06-28
Journal Detail:
Title:  Journal of enzyme inhibition and medicinal chemistry     Volume:  26     ISSN:  1475-6374     ISO Abbreviation:  J Enzyme Inhib Med Chem     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101150203     Medline TA:  J Enzyme Inhib Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  162-8     Citation Subset:  IM    
Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
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