UNDERSTANDING PROTEIN FOLDING AND STABILITY: A COMPUTATIONAL AND EXPERIMENTAL AP

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to use small-angle x-ray scattering to study the character of unfolded proteins, a long standing problem with important implications for understanding the mechanisms of protein folding and the factors that determine protein stability. Although numerous investigators have used SAXS and other techniques to study unfolded proteins, the interpretation of the results has usually been limited to comparisons of scattering data with predictions from highly idealized models that do not account explicitly for excluded volume effects or interactions with the solvent. For this reason, as well as others, there remains a great deal of uncertainty and controversy about the nature of unfolded proteins. To address this difficulty, we have designed a set of experiments that with enable us to directly compare the observed scattering profiles with those we predict from computationally-generated ensembles of explicit conformations based on real amino acid sequences.