Characterizing Receptor Flexibility to Predict Mutations That Lead to Human Adaptation of Influenza Hemagglutinin.

A key step in the emergence of human pandemic influenza strains has been a switch in binding preference of the viral glycoprotein hemagglutinin (HA) from avian to human sialic acid (SA) receptors. The conformation of the bound SA varies substantially with HA sequence, and crystallographic evidence suggests that the bound SA is flexible, making it difficult to predict which mutations are responsible for changing HA-binding preference. We performed molecular dynamics (MD) simulations of SA analogues binding to various HAs and observed a dynamic equilibrium among structurally diverse receptor conformations, including conformations that have not been experimentally observed. Using one such novel conformation, we predicted─and experimentally confirmed─a set of mutations that substantially increased an HA's affinity for a human SA analogue. This prediction could not have been inferred from the existing crystal structures, suggesting that MD-generated HA-SA conformational ensembles could help researchers predict human-adaptive mutations, aiding surveillance of emerging pandemic threats.

The scientific impact of nations: journal placement and citation performance.

International collaboration is becoming increasingly important for the advancement of science. To gain a more precise understanding of how factors such as international collaboration influence publication success, we divide publication success into two categories: journal placement and citation performance. Analyzing all papers published between 1996 and 2012 in eight disciplines, we find that those with more countries in their affiliations performed better in both categories. Furthermore, specific countries vary in their effects both individually and in combination. Finally, we look at the relationship between national output (in papers published) and input (in citations received) over the 17 years, expanding upon prior depictions by also plotting an expected proportion of citations based on Journal Placement. Discrepancies between this expectation and the realized proportion of citations illuminate trends in performance, such as the decline of the Global North in response to rapidly developing countries, especially China. Yet, most countries' show little to no discrepancy, meaning that, in most cases, citation proportion can be predicted by Journal Placement alone. This reveals an extreme asymmetry between the opinions of a few reviewers and the degree to which paper acceptance and citation rates influence career advancement.