The M2 proton channel of influenza A (AM2) and B (BM2) have a highly conserved function motif, considered as the effective target. As yet, there is no effective drug against BM2. Research showed that AM2 channel blocker, amantadine (AMT), was able to bind to BM2 channel, but AMT lacked inhibition against BM2. Nevertheless, the study of the binding but ineffective mode of AMT to BM2 is challenging. To resolve the challenge and obtain more information for drug design of inhibitors targeting BM2, multiple molecular dynamics simulations were performed. We discovered AMT mainly adopted up binding mode in BM2, involved in a transition flipping from down mode to up mode. Furthermore, we discovered a new key factor to explain ineffective inhibition of AMT to BM2 because of the unmatched spatial geometry between AMT and BM2. Our work could enrich structural feature information on BM2 and provide a new perspective for rational drug design of anti-influenza B.