posted on 2017-01-27, 13:49authored byAntonios Drakopoulos, Christina Tzitzoglaki, Chulong Ma, Kathrin Freudenberger, Anja Hoffmann, Yanmei Hu, Günter Gauglitz, Michaela Schmidtke, Jun Wang, Antonios Kolocouris
Recent findings from solid state
NMR (ssNMR) studies suggested
that the (R)-enantiomer of rimantadine binds to the
full M2 protein with higher affinity than the (S)-enantiomer.
Intrigued by these findings, we applied functional assays, such as
antiviral assay and electrophysiology (EP), to evaluate the binding
affinity of rimantadine enantiomers to the M2 protein channel. Unexpectedly,
no significant difference was found between the two enantiomers. Our
experimental data based on the full M2 protein function were further
supported by alchemical free energy calculations and isothermal titration
calorimetry (ITC) allowing an evaluation of the binding affinity of
rimantadine enantiomers to the M2TM pore. Both enantiomers have similar
channel blockage, affinity, and antiviral potency.