9729539 Mayo Characterizing partially-folded and particularly unfolded states of proteins and peptides has been problematic given their transient nature. 13C/15N NMR relaxation is particularly well suited for investigating these states. This project will study backbone and side-chain motions of amino acid residues in unfolded, partially-folded and well-structured peptides by using 13C and 15N NMR relaxation and motional model analyses. The peptides for study are three partially-folded peptides which show conformational preferences in water: (-hairpin (12mer), (-sheet (20mer) and helix (18mer), and a zinc finger peptide (31 residues) Sp1f2 which can be examined in a well-structured native state (1:1 complex with zinc) having both (-sheet and helical structure and in an "unfolded" state (apopeptide without zinc). The relatively small size of these peptides makes them ideal in terms of synthesis, selective 13C/15N isotopic enrichment, and experimental investigation. This project stands apart from previous NMR dynamics studies in that it will use both auto- and cross-correlation parameters from all available motional vectors (backbone and side-chain) and various rotational models and model free approaches to provide a detailed description of motional dynamics in terms of bond rotational restrictions and correlations and motional geometry. The significance of this research lies in characterizing the internal motions in unfolded, partially-folded and well-structured peptides. This information will provide a better understanding of changes which occur on transition from the unfolded to the folded state of a protein and is crucial to solving the protein folding problem. In addition, this research will increase general knowledge of protein dynamics and contribute to the development of better motional models for analysis of NMR relaxation and structural data. ***
