Multi-State Allosteric Behavior in Tuned Thermal Mechanical Networks

Mechanical spring networks have shed insight on allosteric regulation in proteins from a mechanical perspective, particularly on single-state mechanisms of allostery. There, allostery can be understood in terms of small, low-frequency vibrations around a single energy minimum. However, early theories(MWC, J. Mol. Biol. 12, 88 (1965))and observations(Ashkinadze et al., Nat. Commun. 13, 6204 (2022)) suggest that a different “multi-state” mechanism of allostery can also be found in proteins, in which the protein fluctuates among two or more energy minima. Here we tune mechanical networks to attain multi-state allostery at nonzero temperature. Our results highlight the role of thermal noise, giving new insight into how biological functions emerge and persist in noisy environments.