A study to elucidate the thermodynamic situation of transfer Ribonucleic Acids (tRNA) in aqueous solution is proposed. The study will provide thermodynamic data related to the interaction between nucleic acids and the aqueous environment and to the structure stability and interactions of tRNA in solution. Such information should prove useful in developing a more detailed picture of protein synthesis, particularly those aspects which involve tRNA. The proposed project will focus on two aspects of the general problem. The first is the study of the thermodynamic situation of model compounds and tRNA in aqueous solution. Data will be obtained by calorimetric measurements of the heat of solution; heat of dilution of nucleic acids and analogous model compounds in various solvents; and of the thermal unfolding of tRNA under various environmental conditions. Such information is necessary to develop a quantitative understanding of the role which the aqueous environment plays in the structure and stability of tRNA. The second aspect will include studies of the interaction of specific tRNAs with Mg ions, neutral salt, and amino acid specific synthetases. Relevant data will be obtained from equilibrium spectrophotometric studies and from microcalorimetric experiments. The purpose of such studies will be to develop self-consistent thermodynamic models for the reactions. If the general validity of these models is established, extension of thermodynamics studies of tRNA to such areas as condon-anticondon recognition and tRNA-ribosome interactions will be possible. BIBLIOGRAPHIC REFERENCES: T. Sturgill and R. Biltonen, "Macromolecule-Ligand Interactions: Moment Analysis of Derivative Binding Isotherms". Biopolymers 15,000 (1976). Donald Mountcastle and Rodny Biltonen, "Analytical Use of Continuous Exponential Concentration Gradients: Application to Spectrophotometric and Calorimetric Detectors". Biopolymers 15,000 (1976).