MD studies on neuraminidase for probing binding pose of its inhibitors

摘要

Influenzal neuraminidase (NA) has proven to be potential drug target in designing anti-influenza drugs. The active site residues of group-1 and group-2 NA exhibit similarities, such that as structure-based drug design on group-2 NA has given potential anti-influenza drugs showing activity against group-1 as well as group-2 NA. The 150 (Gly147 to Asp151)-loop of NA has been reported to be the cause for the structural differences in the group-1 and group-2 NA enzymes. A cavity arises from an open conformation of the 150 loop which closes upon ligand binding has been reported for group-1 NA. Also recent studies have illustrated that mutation not only causes variation in the active site geometry but also changes the binding orientation of the NA inhibitors. To understand and examine the dynamic nature of ligand binding to NA, we have performed molecular dynamics simulations on NA. The docking study for the reported influenza inhibitors has been performed on averaged structure obtained from three minimum energy conformations of molecular dynamics (MD) trajectory. These results were compared with docking studies done on reported crystal structure of NA (PDB ID 3B7E). The information obtained from these studies can be used for the rational design of novel NA inhibitors.