Thermodynamic projection of the antibody interaction network: the fountain energy landscape of binding

The complexity of the adaptive immune system in humans is comparable to that of the central nervous system in terms of cell numbers, cellular diversity and the network of interactions between components. While the application of molecular biological methods and bioinformatics has brought about an ever deepening and sharpening static description of the molecular and cellular components of the system, a unifying theoretical understanding of the laws governing the dynamics of the system is still lacking. We have recently developed a quantitative model for the description of antibody homeostasis as defined by the dimensions of antigen concentration, antigen-antibody interaction affinity and antibody concentration. In this paper we develop the concept of a novel thermodynamic representation of multiple molecular interactions in a system, the fountain energy landscape of binding. We show that the hypersurface of the binding fountain corresponds to the antibody-antigen interaction network projected onto an energy landscape defined by conformational entropy and free energy of binding. We demonstrate that thymus independent and thymus dependent antibody responses show distinct patterns of changes in the energy landscape. Overall, the binding fountain energy landscape concept allows a systems biological, thermodynamic perception of the functioning of the clonal humoral immune system. 2 peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/124503 doi: bioRxiv preprint first posted online Apr. 5, 2017;