Researcher Resources Member Profiles C. Robert Matthews, Ph.D.
C. Robert Matthews, Ph.D.
Professor, University of Massachusetts Medical School
Faculty Appointment(s) In: Biochemistry and Molecular Pharmacology
Other Affiliation(s): Center for AIDS Research, Graduate School of Biomedical Sciences, Program in Bioinformatics and Integrative Biology
Lazare Research Building, Rm 928
364 Plantation Street
Worcester, Massachusetts 01605
Phone: 508 856-2251
E-mail:
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Keywords: Protein Folding, Biophysics, Biochemistry
Research Interests
Solving the Protein Folding Problem
Determining the mechanism by which the amino acid sequence of a protein directs the rapid and efficient folding to the native, functional conformation is one of the most challenging problems in molecular biophysics. Development of a folding code that specifies the three-dimensional structure adopted by a given sequence would complement the genetic code and complete the central dogma of molecular biology (DNA ® RNA ® Amino Acid Sequence ® Functional Protein). Advances in genetic engineering, peptide synthesis and spectroscopy provide new insight into the structure and stability of folding intermediates, i.e., partially folded forms that contain essential clues on the mechanism.
In our laboratory we use these new technologies in a broad-ranging effort to solve the protein folding problem. By combining site-directed mutagenesis, protein fragmentation or peptide synthesis with biophysical techniques (including absorbance, fluorescence, circular dichroism and NMR spectroscopies), insights into the folding mechanisms of several representative proteins are being obtained. Current efforts are focused on the folding of several monomeric proteins, including the a-subunit of tryptophan synthase from E. coli, dihydrofolate reductases from E. coli and human, and the ras p21 protein from human. The folding of oligomeric proteins and the factors influencing the association of protein chains are also being addressed with studies on the tryptophan aporepressor from E. coli, carbonic anhydrase from M. thermophila, and a peptide model system, the leucine zipper domain of the yeast transcriptional activator, GCN4.