Efforts to develop improved techniques for the growth of protein crystals have been driven by the need to determine protein crystal structures for medical and pharmaceutical applications. The inability to routinely grow single crystals of sufficient size and quality is a major roadblock to the wider application of protein crystallography. We propose to investigate the use of temperature as a control parameter in the crystal growth of proteins and other biomolecules. Methodology will be developed using amino acid and simple peptide solutions. Proteins suitable for temperature programmed growth experiments will be selected based upon either published solubility data or data obtained during the course of the proposed research. We also propose to investigate the nonlinear optical response of amino acid, peptide and protein solutions near saturation. The purpose of the nonlinear optical investigation is to determine if there are changes in fast (100 fs - 100 ps) structural fluctuations which occur as the biomolecules begin to aggregate in the initial stages of crystal growth. It may then be possible to study the onset of nucleation by looking at the dynamics of these fluctuations during the crystal growth process.
