Allosteric linkages that emulate a molecular motor enzyme

In this study, I describe a model in which mechanical linkages dynamically interact in a stepwise and reversible manner, and use it to model the chemical cycle and lever arm action of the biomolecular motor myosin. Myosin is emulated using a series of multivalent chemical reactions between a linkage enzyme and four reactants: a cleaveable fuel, two cleavage products, and ligand. Geometric coupling between the fuel and ligand binding sites--an analog for negative allosteric coupling--allows reaction sequences similar to nucleotide exchange to take place that in turn drive the "strokes" of the machines lever arm. Cyclic chemical behavior is demonstrated by stochastic simulation, and mechanical activity by a series of logical arguments. I show how a reciprocal and nonreciprocal conformational cycle emerge from the allosteric rules designed to achieve chemical cycling, and how the non-reciprocal cycle can break directional symmetry along a track like structure. A dimeric construct is used to demonstrate how directed motion can be designed by inhibition of the reciprocal cycle and reinforcement of the non-reciprocal cycle, through allosteric feedback between the units of the dimer. By showing how the chemomechanical cycle of a biomolecular motor can be recreated with simple geometric and chemical principles, this work may help advance the rational design of allosteric mechanisms, and the development of synthetic molecular motors.