Why bound amantadine fails to inhibit proton conductance according to simulations of the drug-resistant influenza A M2 (S31N).

ABSTRACT: The mechanisms responsible for drug resistance in the Asn31 variant of the M2 protein of influenza A are not well understood. Molecular dynamics simulations were performed on wild-type (Ser31) and S31N influenza A M2 in the homotetramer configuration. After evaluation of 13 published M2 structures, a solid-state NMR structure with amantadine bound was selected for simulations, an S31N mutant structure was developed and equilibrated, and the native and mutant structures were used to determine the binding behavior of amantadine and the dynamics of water in the two channels. Amantadine is stable in the plugging region of wild-type M2, with the adamantane in contact with the Val27 side chains, while amantadine in S31N M2 has more variable movement and orientation, and spontaneously moves lower

SUBMITTER: Gleed ML 

PROVIDER: S-EPMC4306489 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature