Understanding the chiral recognitions between neuraminidases and inhibitors: Studies with DFT, docking, and MD methods

摘要

The chiral recognitions between various neuraminidases (NA) and 5-[(1R,2S)-1-(acetylamino)-2- methoxy-2-methylpentyl]-4-[(1Z)-1-propenyl)-(4S, 5R)]-D-proline (BL) stereoisomers have been theoretically studied. The zwitterions of BL are responsible for the bioactivities, and electrostatic rather than van der Waals (vdW) contributions play a significant role. With the presence of NA proteins, the orders of relative stabilities of the BL stereoisomers are greatly altered; meanwhile, the ranges are significantly enlarged, ensuring the respective recognitions of the BL9z, BL3z, BL2z, and BL1z stereoisomers by the N1, N2, N9 subtype, and B type NA proteins. It is mainly due to geometric complementarities of the NA active sites with the BL carboxyl and propenyl groups. The recognitions of proteins with chiral ligands are rather targeted, even applicable to N2 and N9 with high structural similarities. Thus, the significance of chirality is addressed for the designs of anti-influenza drugs, which aids our understanding of chiral recognitions between proteins and ligands.