講座內容：I will give an introduction to the long-standing O-ring theory and a refined version called double waterexclusion for modelling protein binding sites. The O-ring hypothesis stated that a binding hotspot is usually surrounded by a ring of residues which have insignificant contribution to the binding free energy. Our double water exclusion hypothesis states that the binding hotspot is the cluster of biclique residues that are not very much exposed to bulky water. In this talk, I also describe an extended version, called tripartite model, for the computational implementation of protein binding hotspots. This protein-water-protein tripartite model is novel as immobilized water molecules are included in thisgraph model. I will illustrate how this model is used to predict proteinbinding hotspots in binding interfaces, and why the mutation of the 2009 H1N1 virus did not cause a bigger pandemic disaster than the Spanish Flu pandemic in1918.