Binding hot spots and amantadine orientation in the influenza a virus M2 proton channel.

ABSTRACT: Structures of truncated versions of the influenza A virus M2 proton channel have been determined recently by x-ray crystallography in the open conformation of the channel, and by NMR in the closed state. The structures differ in the position of the bound inhibitors. The x-ray structure shows a single amantadine molecule in the middle of the channel, whereas in the NMR structure four drug molecules bind at the channel's outer surface. To study this controversy we applied computational solvent mapping, a technique developed for the identification of the most druggable binding hot spots of proteins. The method moves molecular probes--small organic molecules containing various functional groups--around the protein surface, finds favorable positions using empirical free energy functions, cluste

SUBMITTER: Chuang GY 

PROVIDER: S-EPMC2776279 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature