Thermodynamic projection of the antibody interaction network: The fountain energy landscape of molecular interaction

The adaptive humoral immune system of vertebrates functions by evolving a huge repertoire of binding proteins, which target potentially all molecules that come into contact with developing B cells. The key to endowing these binders with immunological activity is the adjustment of antibody structure and affinity against molecular targets. As a result, antibodies with a wide range of affinities and specificities evolve during the lifetime of an individual. A recently developed a quantitative model for the description of antibody homeostasis suggests that a quantitative network can describe the dynamic antibody-antigen interaction space. Here, this molecular interaction space is projected onto an energy landscape defined by entropy and free energy of binding. I introduce the concept of binding fountain energy landscape, which allows the thermodynamic representation of binding events and evolution of binding paths of multiple interactions. I further show that the hypersurface of the binding fountain corresponds to the antibody-antigen interaction network. The binding energy landscape identifies unique properties of B1 cells and natural antibodies, and distinct patterns of thymus independent and thymus dependent antibody responses. Overall, the fountain energy landscape concept of molecular interactions allows a systems biological, thermodynamic perception and description of the functioning of the clonal humoral immune system and generally describes protein evolution in thermodynamic space. 1