SMALL SEGMENTAL REARRANGEMENTS IN THE MYOSIN HEAD CAN EXPLAIN FORCE GENERATION IN MUSCLE

Poisson-Boltzmann calculations of the distribution of electrostatic po tentials around an actin filament in physiological-strength solutions show that negative isopotential surfaces protrude into the solvent, Ea ch protrusion follows the actin two-start helix and is located on the sites implicated in the formation of the actomyosin complex, Molecular dynamic calculations on the S1 portion of the myosin molecule indicat e that in the presence of ATP the crystallographically invisible loops (comprising residues 624-649 and 564-579) remain on the surface, wher eas in the absence of ATP they can move toward the actin-binding sites and experience electrostatic forces that range from 1 to 10 pN. The m olecular dynamics calculations also suggest that during the ATP cycle there exist at least three states of electrostatic interactions betwee n the loops and actin. Every time a new interaction is formed, the str ain in the myosin head increases and the energy of the complex decreas es by 2kT to 5kT. This can explain muscular contraction in terms of a Huxley-Simmons-type mechanism, while requiring only rearrangements of small mobile S1 segments rather than the large shape changes in the my osin molecule postulated by the conventional tilting head model.