Molecular Movements in Bioenergy Transduction

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This application proposes an international cooperation among three American and three Soviet laboratories. The scientific objective is to define the relative movements between myosin subfragment 1 (S-1) and actin (in complex) under the influence of ATP hydrolysis going on in S-1. These movements, underlying muscle contraction and some cell motility, are thought to accomplish energy transduction (free energy of ATP hydrolysis to mechanical (force x distance) work). Optically-detected molecular probes are to be used in pairs, either to detect correlated re-orientation or to detect change in scalar distances, the purpose being to decide whether the movements in transduction are a global rotation of S-1 caused by very small internal displacements (present "standard model") or whether internal movements encompass most of S-1 (as in interdomain movement). Efforts will be made---using differential scanning calorimetry circular dichroism---to obtain indications of domain structure, and also to examine the effect of crosslinks on the putative movements of these domains. Attempts also will be made to develop both physical (S-1 on oriented pure F-actin) and molecular graphic models in order to simplify the foregoing studies. Besides the six senior investigators, several students and young associates would participate in this work. The principal significance of this proposal is basic. Since no biological energy transducer has yet been explained, the possibility of discovering design features also may be of practical interest.