The structure of myosin subfragment-1 complexed with nucleotides, nucleotide analogues, synthetic fragments of actin and assembly defective actin mutants will be analysed by X-ray crystallography. The project will involve the crystallization of myosin S1 in the presence of these molecules, followed by X-ray diffraction data collection using conventional and synchrotron sources, and the determination of the resultant conformational changes with difference Fourier, molecular replacement and isomorphous replacement techniques. These structural studies will show how the myosin head interacts with nucleotides and actin, and will improve the understanding of the molecular basis of motility, specifically the conformational transitions in the muscle fibers which occur during contraction.