Molecular mechanism of force generation in biological systems. Molecular nanomotors

 

All life systems from bacteria to humans are able to convert chemical energy into mechanical work and produce the directed movement. The elucidation of mechanisms of energy transduction by biological molecules would help to understand the physical principles of life. The skeletal muscle is an example of efficient, highly organized biological engine. Muscle contraction occurs in result of relative sliding of two (thick and thin) filament systems composed mainly by two proteins – myosin and actin. The energy for contraction is derived from small organic molecule ATP. However, the mechanism of coupling of ATP hydrolysis with force production is still obscure. My research is focused on the study of interactions of myosin with actin and ATP by various physical and biochemical methods. The main findings of my work are: ATP induced unbending of myosin molecule; the binding of myosin to actin filament occurred in multiple steps and might be presented as rolling of myosin head along the actin filament. We performed a computational docking of myosin with F-actin and found two bound states with a minimal potential energy: one corresponding of the interaction of myosin with two actins and the second – with three actins. The obtained results provide a molecular basis for the rolling model originally proposed by A. Huxley and R. Simmons in 1971. Ordered formation of acto-myosin interface might generate force and directed movement. I plan to continue fluorescence spectroscopy and stopped flow cross-linking studies of dynamics of protein-protein interface.