UNASSIGNED: Influenza @entity689 (NA) is a pivotal target for @entity1800 control. However, the accumulating of mutations compromise the efficacy of NA inhibitors. Thus, it is critical to design new drugs targeted to different motifs of NA. Recently, a new motif called 340-cavity was discovered in NA subtypes close to the @entity460 binding site. The presence of @entity460 is known to influence NA activity and thermostability. Therefore, the 340-cavity is a putative ligand-binding site for affecting the normal function of NA. In this study, we performed molecular dynamics simulations of different NA subtypes to explore the mechanism of 340-loop formation. Ligand-binding site prediction and fragment library screening were also carried out to provide evidence for the 340-cavity as a druggable pocket. We found that residues G342 and P/R344 in the 340-loop determine the size of the 340-cavity, and the @entity460 ion plays an important role in maintaining the conformation of the 340-loop through contacts with G345 and Q347. In addition, the 340-cavity is predicted to be a ligand-binding site by metaPocket, and a sequence analysis method is proposed to predict the existence of the 340-cavity. Our study shows that the 340-cavity is not an occasional or atypical domain in NA subtypes, and it has potential to function as a new hotspot for influenza drug binding.

The 340-cavity in XXXX provides new opportunities for influenza drug development: A molecular dynamics simulation study.

@entity689 :: ('4758', 'Gene') :: ['neuraminidase'] @entity1800 :: ('MESH:D014777', 'Disease') :: ['viral infection'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium']
@entity689 :: (4758,Gene) :: ['neuraminidase']
