Evaluation on the receptor-binding preference and drug resistance of H9N2 influenza viruses

The enzootic and zoonotic nature of H9N2 avian influenza viruses pose a persistent threat to global poultry industry and human health. This particular subtype influenza virus raises public concerns because it possesses human receptor specificity. In this study, four H9N2 virus strains clustered into the G57-like viruses preferentially bound to SAα2,6 receptors as demonstrated in the results from the receptor-binding assay. The molecular dynamic simulation showed that HAQ226L substitution of H9N2 viruses may alter the conformation of the 220-loop of hemagglutinin (HA) and thus optimize the contacts between HA and human receptors, thereby increasing the preference for α2,6-linkages. The acquisition of an additional N-glycosylation site at position 264 close to the enzyme active sites of neuraminidase of H9N2 viruses induced the loss of hydrogen bonding between 276E at the enzyme active sites and Zanamivir and further led to occurrence of Zanamivir-resistant of viruses. This study shows the relationship between the conformational changes due to amino acid variations and viral biological phenotypes, which emphasizes the necessity for monitoring the continual evolution of H9N2 viruses and comprehensively assessing their potential zoonotic threat.

Low-Frequency Protein Motions Coupled to Catalytic Sites

This review examines low-frequency vibrational modes of proteins and their coupling to enzyme catalytic sites. That protein motions are critical to enzyme function is clear, but the kinds of motions present in proteins and how they are involved in function remain unclear. Several models of enzyme-catalyzed reaction suggest that protein dynamics may be involved in the chemical step of the catalyzed reaction, but the evidence in support of such models is indirect. Spectroscopic studies of low-frequency protein vibrations consistently show that there are underdamped modes of the protein with frequencies in the tens of wavenumbers where overdamped behavior would be expected. Recent studies even show that such underdamped vibrations modulate enzyme active sites. These observations suggest that increasingly sophisticated spectroscopic methods will be able to unravel the link between low-frequency protein vibrations and enzyme function.

Challenges in constructing accurate methods for hydrogen transfer reactions in large biological assemblies: rare events sampling for mechanistic discovery and tensor networks for quantum nuclear effects

We present two methods that address the computational complexities arising in hydrogen transfer reactions in enzyme active sites.

The role of Brønsted base basicity in estimating carbon acidity at enzyme active sites: a caveat

Using the pKE-BH+a value of the Brønsted base catalyst in the enzyme–substrate complex can overestimate the extent to which an enzyme lowers the substrate's pKC–Ha value.