2016.10.21. Modulation of cell-virus adhesion

2019-07-07 00:35:57 0



题 目: Modulation of cell-virus adhesion

报告人: Huafeng Xu, Ph.D.

Senior scientist, D. E. Shaw Research

时 间: 2016年10月21日(周五),10:00-11:30

地 点: 化学与分子工程学院A717报告厅

主持人: 来鲁华 教授


Adhesion to host cells is a key step in infection by many viruses, including the influenza virus.Such adhesion is typically the result of specific molecular binding between receptors and ligands on the surfaces of cells and viruses, respectively.The adhesion of influenza viruses to cells, for example, is mediated by the binding between hemagglutinins on the virus and sialic acid receptors on the cell.Here, we present two studies of cell–influenza virus adhesion.First, we have characterized the structures and thermodynamics of hemagglutinin–sialic acid binding using molecular dynamics simulations and biophysical experiments.Our results suggest that sialic acid receptors bind to hemagglutinin variants in a dynamic ensemble of diverse conformations—including novel conformations not yet observed in X-ray crystallography—and that this conformational plasticity may facilitate the adaptation of avian influenza viruses for human infection.Second, we have developed a quantitative model of adhesion that accurately predicts adhesion affinity from the numbers of available receptors and ligands and their individual binding affinity.Our model provides an estimate of the affinity range of hemagglutinin–sialic acid receptor binding necessary for the influenza virus to successfully infect host cells, and predicts that hemagglutinin inhibitors of relatively modest affinity can dramatically reduce influenza virus adhesion to host cells, suggesting that such inhibitors, if discovered, may be viable therapeutic agents against influenza.


Huafeng got his introduction to chemistry in Beijing University.He studied with Prof. Bruce Berne in Columbia University and earned a Ph.D. in chemistry.After a two-year stint in a biotech start-up, 3-Dimensional Pharmaceuticals (which was later acquired by Johnson & Johnson), he studied with Prof. Ken Dill in University of California, San Francisco.He then joined D. E. Shaw Research and had remained there since.His current research interests include methods of free energy calculations and their applications, modulation of biological adhesions, epitope-specific elicitation and affinity maturation of antibodies, and protein design.