Multivalency in DNA-confined spaces

• Applicant: Professorin Dr. Barbara Saccà
• Subject Area: Biological and Biomimetic Chemistry
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 463419602

Nature masters the building of complex macromolecular assemblies and the actuation of highly-energetic processes employing multiple forces coordinated in space and time. Multivalent binding in a confined environment is therefore a natural strategy to overwhelm the underlying Brownian noise of the cell environment, enabling molecular forces to become effective. The energetic advantage of multivalency, i.e. the binding of identical and linked ligands to the receptor sites of a target protein, mostly relies on the favorable entropic contribution resulting from the degeneracy of the system. On the other hand, physical barriers imposed by the spatial confinement of the reaction within specialized compartments, decreases the probability of molecular disorder and thus the entropy of the system. Although a certain number of studies have been performed to understand the energetic contributions given by each of the two phenomena, i.e. multivalency and spatial confinement, in distinct systems, their combined effect within one single macromolecular complex is still largely unexplored. The purpose of the present project is to understand how multivalency and spatial confinement act together in defining the free-energy of the system and why this combination results advantageous in natural processes.

• DFG Programme: Research Grants