Design of multivalent ligand is significant in restraining the interaction involved in the binding of influenza virus to its host cell. This molecular dynamics (MD) simulation study aims to study the mode of binding of dimeric NeuNAc analogues coupled by different nano-spacers into the multimeric binding sites of neuraminidase and haemagglutinin of influenza A H5N1 virus. In total, 80 NeuNAc analogue dimers were modeled and docked against the binding sites of neuraminidase and haemagglutinin. The top scoring complexes such as neuraminidase – 2-keto-3-deoxy-D-glycero-d-galacto-nononic acid (or KDN) dimer coupled by 1-nano-linker, neuraminidase – KDN dimer linked by CH-C1 nanospacer, haemagglutinin – KDN dimer connected by CH-C1 nano-spacer and haemagglutinin – KDN dimer joined by CH-N1 nano-spacer were taken in for the conformational investigation by molecular dynamics (total 80ns) in aqueous environment. The potential energy profile, RMSD, RMSF, protein – ligand contacts and intermolecular hydrogen bond interactions suggest that the complexes were stable throughout the trajectory of MD simulations. The ligand torsion report was calculated for each rotatable bond of dimers of NeuNAc analogues which were bound to target proteins such as neuraminidase and haemagglutinin. The binding energy and conformational study of the complexes reveal that the nano-spacer coupled dimers of NeuNAc analogues may be used as potential candidates for designing multivalent drugs to inhibit neuraminidase and haemagglutinin and perhaps to prevent the viral spread. | Multivalent interactions of Nano-spaced dimers of N-acetylneuraminic acid analogues complex with H5N1 influenza viral Neuraminidase and Haemagglutinin - A molecular dynamics investigation
