Abiotic Energy Molecules
Myosin is a motor protein that is responsible for generating force and motion in eukaryotes. The fuel for myosin is adenosine triphosphate (ATP). At the most fundamental level, the free-energy released by ATP hydrolysis in muscle myosin’s active site induces a local stretch or distortion in one or more chemical bonds. This distortion initiates large conformational changes, which lead to force-generation and thus mechanical work.
From this fundamental point of view, the free energy released by any molecule could induce those changes in myosin and transduce into force and motion. Achieving such systems where abiotic molecular batteries serve the role of ATP will provide us unprecedented opportunities in the design and development of novel chemo-mechanical energy transduction materials that mimic motor proteins. These systems will also allow us to investigate fundamental questions related to free-energy transfer and generation of force in motor proteins.
We use positional isomerism of azo-benzene based triphosphates as a simple and powerful tool to control the molecular motor of muscle, myosin. Using three isomers of a synthetic non-nucleoside triphosphate, we demonstrated that myosin’s force and motion generating capacity can be dramatically altered at both the ensemble and single molecule levels. By correlating our experimental results with computation, we can find out how that each isomer exerts intrinsic control by affecting distinct steps in myosin’s mechano-chemical cycle.
Woodward, M.; Ostrander, E.; Jeong, S. P.; Liu, X.; Scott, B.; Unger, M.; Chen, J.; Venkataraman, D.; Debold, E. P. “Positional Isomers of a Non-Nucleoside Substrate Differentially Affect Myosin Function,” Biophysical J. 2020, 119, 567-580. [Link]