The Effect of Amino Acid Replacements on the Folding        and Stability of Dihydrofolate Reductase
{'Code': '08070400', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'MCB', 'LongName': 'Div Of Molecular and Cellular Bioscience'}}
{'SignBlockName': 'Marcia Steinberg', 'PO_EMAI': None, 'PO_PHON': None}
The goal of this research is to understand the mechanisms by                    which a protein folds spontaneously to a unique 3-dimensional                   conformation.  Presumably, all the information required for                     folding is contained in the primary amino acid sequence.                        Thus, changes at key positions in the sequence could have                       profound effects on folding, which can be identified and used                   to elucidate the nature of the folding process.                                                                                                                 Dihydrofolate reductase from E.coli is the model protein                        chosen for study.  Its gene has been cloned and its                             3-dimensional structure is known.  Mutants will be generated                    by mutagenesis directed at sites believed to be important in                    the folding reactions.  Equilibrium and kinetic studies will                    be carried out on the folding/unfolding transition in wild                      type and mutant proteins using ultraviolet, fluorescence,                       circular dichroism and NMR spectroscopy.  The results                           will be fit to simple models, and conclusions drawn regarding                   the structural features that are critical to folding.  From                     such studies the rules that govern folding may eventually                       emerge, so that it will become possible to make predictions                     on the function of a protein based on its primary structure.
{'FirstName': 'C Robert', 'LastName': 'Matthews', 'PI_MID_INIT': None, 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'C Robert Matthews', 'EmailAddress': 'c.robert.matthews@umassmed.edu', 'NSF_ID': '000383679', 'StartDate': '09/01/1987', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
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[{'Code': '1144', 'Text': 'Molecular Biophysics'}, {'Code': '9120', 'Text': 'CROSS-DIRECTORATE PROGRAMS'}, {'Code': '9145', 'Text': 'SPECIAL PROGRAMS-RESERVE'}]
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