The recently discovered 340-cavity in influenza neuraminidase (NA) N6 and N7 subtypes has introduced new possibilities for rational structure-based drug design. However, the plasticity of the 340-loop (residues 342-347) and the role of the 340-loop in NA activity and substrate binding have not been deeply exploited. Here, we investigate the mechanism of 340-cavity formation and demonstrate for the first time that seven of nine NA subtypes are able to adopt an open 340-cavity over 1.8 μs total molecular dynamics simulation time. The finding that the 340-loop plays a role in the sialic acid binding pathway suggests that the 340-cavity can function as a druggable pocket. Comparing the open and closed conformations of the 340-loop, the side chain orientation of residue 344 was found to govern the formation of the 340-cavity. Additionally, the conserved calcium ion was found to substantially influence the stability of the 340-loop. Our study provides dynamical evidence supporting the 340-cavity as a druggable hotspot at the atomic level and offers new structural insight in designing antiviral drugs.
Pubmed ID: 32781779 RIS Download
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An open-source program for doing molecular docking.
View all literature mentionsSoftware suite of automated docking tools. Designed to predict how small molecules, such as substrates or drug candidates, bind to receptor of known 3D structure. AutoDock consist of AutoDock 4 and AutoDock Vina. AutoDock 4 consists of autodock to perform docking of ligand to set of grids describing target protein, and autogrid to pre calculate these grids.
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