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

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. I recently developed a quantitative model for the description of antibody homeostasis and suggested that a quantitative network can describe the dynamic antibody-antigen interaction space. Here, I project this molecular interaction space onto an energy landscape defined by conformational entropy and free energy of binding. I introduce the concept of binding fountain energy landscape, which allows the thermodynamic representation of binding events and paths of multiple interactions. I further show that the hypersurface of the binding fountain corresponds to the antibody-antigen interaction network. I propose that thymus independent and thymus dependent antibody responses show distinct patterns of changes in the energy landscape. 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.