Abstract
To eventually construct autonomous molecular machines that are as capable as their biological counterparts, the mechanism of allostery, which still largely cannot be explained at the atomic level, needs to be translated into a set of understandable building principles. In this study, I demonstrate a coarse-grained example of such a translation by using linkages to model the allosteric and catalytic interactions between an enzyme and its four reactants, which include a fuel, two products, and a ligand. I use the system of five linkage molecules to emulate a generic chemical pumping cycle derived from myosin, a molecular motor enzyme that is an archetype of free-energy transduction. The linkage enzyme is constructed around two binding sites - one for the fuel and product, and one for the ligand - that are negatively and allosterically coupled to one another through mutually exclusive geometries that form during binding reactions. Using stochastic simulations, I demonstrate how the design allows for a pair of allosterically triggered dissociations to alternately and cyclically take place at each binding site. The two allosteric reactions are linked together by catalysis, and enable the enzyme to be pushed through a continuous cycle of ligand binding, fuel binding, and product binding. Overall, cycling is driven by the consumption of out-of-equilibrium fuel, but it requires the reciprocating and allosterically controlled dissociations for correct operation. By showing how the chemical cycle of a biomolecular pump can be recreated with simple geometric and chemical principles that encode allosteric mechanisms, this work can help inform the development of more mechanically capable synthetic pumps and motors.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
This version better describes the work in references 14-16 as elastic network models, rather than simply as linkages (Introduction, paragraph four). It also better describes the differences between the models in references 14-16 and the model presented in the manuscript (Introduction, paragraph five).