The highly pathogenic avian influenza strain H5N1 has resulted in 372 confirmed cases of human infection since 2003 with a fatality rate of more than 60 %. Although the H5N1 strain is sensitive to currently approved drugs oseltamivir and zanamivir, which target the viral enzyme neuraminidase (NA), single point mutations have been identified in some NA strains of subtype N1 which confer resistance to both drugs. In this study, crystallographic structures are being used to construct protein-ligand complexes with various N1 mutations for computational modeling. Specifically, all-atom molecular dynamics simulations are being used in an effort to understand the basis of resistance due to H274Y and N294S point mutations. The goal is to determine which interactions are most crucial in the binding site for wildtype N1 and then lost as a result of either mutation. Future goals include virtual screening against N1, specifically targeting the recently reported novel 150-loop cavity, in an effort to discover new drug leads. In light of the potential for a future H5N1 pandemic the need for additional antivirals is paramount.