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How the amino acid sequences of polypeptide chains determine their three dimensional structure is a major unsolved problem in modern biology. Progress in deciphering this second half of the genetic code should lead to major advances in our ability to interpret genome sequences, to design new proteins, and to understand a variety of human protein misfolding diseases. This course attempts to develop the capacity of students to make a contribution toward solving this problem.

The first part of this course will involve lectures, readings database, and discussion questions. We will start by reviewing protein structure and conformation; then proceed to more advanced investigations of the actual mechanisms and sequence control of polypeptide chain folding in vitro; and then consider the intracellular mechanisms, helpers and compartments involved in protein folding within cells.

In the later part of the semester, students will choose a research topic for a term paper. These topics will be on critical areas of current research on protein folding, including applications of medical, biotechnological or computational importance. The substantial findings will be presented to the class in an oral presentation, as at a scientific meeting, with the final paper to be handed in by the last class. Topics to choose from and more detailed instructions will be distributed in mid-semester.

Regular reading assignments will be in Branden and Tooze, Introduction to Protein Structure, 2nd ed.; and Pain, Mechanisms in Protein Folding, 2nd ed. Research papers will also periodically be assigned as well as occasional internet searches. There will be ungraded problems, one graded problem set, an in-class midterm exam, and a final research paper. (Undergraduates and Graduates will be graded independently.)

The general outline of the material covered is:

  • Part 1 - Selected aspects of the 3-D conformations of globular and fibrous proteins.
  • Part 2 - Sequence determinants, kinetics and pathways for the in vitro refolding of proteins.
  • Part 3 - In vivo folding of newly synthesized proteins and their interactions with chaperonins and other helpers; protein misfolding and aggregation; protein folding and human disease.
  • Part 4 - Student research papers.