The emergence and continuing global spread of the highly virulent avian influenza H5N1 has raised concerns of a possible human pandemic. Several approved anti-influenza drugs effectively target the neuraminidase (NA), a surface glycoprotein that cleaves terminal sialic acid residues and facilitates the release of viral progeny from infected cells. The first crystal structures of group-1 NAs revealed that although the binding pose of oseltamivir was similar to that seen in previous crystallographic complexes, the 150-loop adopted a distinct conformation, opening a new cavity adjacent to the active site. Here we show that the 150-loop is able to open into significantly wider conformations than seen in the crystal structures, through explicitly solvated MD simulations of the apo and oseltamivir-bound forms of tetrameric N1. We find that motion in the 150-loop is coupled to motion in the neighboring 430-loop, which expands the active site cavity even further. Furthermore, in simulations of the oseltamivir-bound system, the 150-loop approaches the closed conformation, suggesting that the loop switching motion may be more rapid than previously observed.