Michael H. Hecht
Professor of Chemistry
Ph.D 1984, Massachusetts Institute of Technology
Michael Hecht works on the design novel proteins. We use a mixture of rational design and combinatorial methods: Combinatorial libraries of de novo amino acid sequences can provide a rich source of diversity for the discovery of novel proteins. Randomly generated sequences, however, rarely fold into well-ordered protein-like structures. To enhance the quality of a library, diversity must be focused into regions of sequence space consistent with well-folded structures. We design focused libraries of sequences by constraining the binary pattern of polar and nonpolar amino acids to favor structures that contain abundant secondary structure (alpha-helices and beta-sheets), while simultaneously burying hydrophobic side chains in the protein interior and exposing hydrophilic side chains to the surrounding solvent. We have used these strategies to produce focused libraries of either alpha-helical or beta-sheet de novo proteins. These libraries have successfully produced well-ordered structures, cofactor binding proteins, catalytically active enzymes, self-assembled monolayers, amyloid-like nanofibrils, protein-based biomaterials, and prototype biosensors.