Our objective is to explore the chemical and structural events in myosin during its cyclic interaction with actin and ATP. Through these studies we wish to gain insight into the mechanism of energy transduction and tension generation in muscle. We plan to study the conformational states and transitions in myosin employing chemical modifications of residues essential to the enzymic activity of the protein. Most of the modification experiments will be directed towards the two essential sulfhydryl groups per each myosin head and will probe their separation under a variety of conditions. These studies will be accompanied by attempts to affinity label the active site of myosin with analogs of ADP or ATP. We will try to establish spatial relationship between the active site, the actin site and the essential thiols of myosin. The possible function of the DTNB light chain in the regulation of contraction of striated muscle remains unknown. We plan to compare the metal binding properties of the isolated DTNB chain with those of the intact chain in the parent myosin molecule. In the next stage we will perform chymotryptic digestions of myofibrils to evaluate the relevance of the observed peturbations of the DTNB chain to the contractile process. We also intend to examine the conformational changes on yet another protein - actin. We wish to find out what transitions have to parallel the polymerization process of actin in order to confer on this protein its ability to activate the catalytic power of myosin.