Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to 
fight the flu virus in infected individuals by inhibiting neuraminidase, a flu 
protein responsible for the release of newly synthesized virions. However, 
oseltamivir resistance has become a critical problem due to rapid mutation of 
the flu virus. Unfortunately, how mutations actually confer drug resistance is 
not well understood. In this study, we employ molecular dynamics (MD) and 
steered molecular dynamics (SMD) simulations, as well as graphics processing 
unit (GPU)-accelerated electrostatic mapping, to uncover the mechanism behind 
point mutation induced oseltamivir-resistance in both H5N1 "avian" and H1N1pdm 
"swine" flu N1-subtype neuraminidases. The simulations reveal an electrostatic 
binding funnel that plays a key role in directing oseltamivir into and out of 
its binding site on N1 neuraminidase. The binding pathway for oseltamivir 
suggests how mutations disrupt drug binding and how new drugs may circumvent the 
resistance mechanisms.