This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We propose an integrated approach combining state-of-the-art computational and experimental solid-state NMR methodologies for characterization of nanoscale structure and dynamics of novel peptide and protein biomaterials. This approach is designed to overcome the limitations of the more traditional spectroscopic and microscopic techniques applied for analysis of biomaterials. Specifically, we will develop solid-state NMR based protocols for characterization of macromolecular structure, dynamics and cross-links in peptide hydrogel assemblies. We will continue development and refinement of polarizable, or non-additive, force fields applicable to statistical mechanics ?based approaches for modeling peptide-peptide and peptidesolvent (water) interactions. We will establish protocols for the characterization of polarizable (non-additive) force fields through ab initio prediction of relative solvation free energetics of small peptides and amino acid analogues;methods for efficient free energy calculations using polarizable force fields. Our initial work will focus on peptide hydrogels developed by Schneider and Pochan (subproject 2). Peptide hydrogels are promising scaffolds for liver tissue regeneration. These materials represent ideal model systems for development of experimental solid-state NMR and computational methods for structure and dynamics analysis of noncrystalline peptide and protein materials as they have been extensively characterized on macroscopic and mesoscopic scales but detailed structure and dynamics information is not available. Gaining atomic-level structural information is critically needed as it will guide the design of the next generation hydrogel materials with tunable properties for clinical applications. We will characterize the lateral and facial assembly of peptide hydrogels, address their backbone and sidechain dynamics, and probe the water motions. The experimental and computational methodologies established on hydrogels will be generally suited (but not limited) to studies of a broad range of peptide and protein biomaterials developed in other subprojects of this COBRE program. In a broader sense, we expect our approach to be beneficial to the entire biomaterials community as it addresses the current need for new atomic-scale resolution methods capable of probing complex amorphous biomaterials intractable by conventional structural techniques.
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