mechano-kinetic computer models
Areas of expertise
My research focuses on how muscles contract. The structural events by which myosin heads projecting from the surface of thick filaments interact with actin of the thin filaments to generate force is being dramatically illuminated as the atomic structures of new myosin conformations are solved. Moreover, the kinetics of the steps of the cross-bridge cycle (attachment, power stroke, detachment and recovery) are known at least in solution. However, it is crucial to determine whether such a cycle can account for the mechanical properties of contracting muscle (its force, power output, ATP usage, velocity of shortening and efficiency). I have been testing this by developing mechano-kinetic computer models of the cross-bridge cycle. The effect of strain on the steps are specified using transition-state theory incorporating new understanding of how force dissociates protein complexes. The models are able to account for the experimental steady-state force-velocity relation of skeletal muscle.