Concepts of Protein Folding

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Concepts of Protein Folding

• Thermodynamics and Kinetics

http//www.biochem.oulu.fi/juffer/
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Overview of course

• Total of 14h, 1.5 credit points.
• Three main topics
• Structural stability of protein structures.
• Kinetics of protein folding.
• Folding pathways and energy landscapes.
• Both water-soluble and membrane proteins.
• Examination Article presentation.
• Credits points only examination plus attend 5 of
  7 lectures (2x45 minutes).

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Theory of protein folding (1)

• Understanding biological processes requires
  insights from physical chemistry.
• Both local structure and global three dimensional
  structure can be reached from sequence only
  (Afinsen)
• Remarkable given the complexity of protein
  structures.
• Early progress
• Importance of the hydrophobic effect (Kauzmann).
• Analysis of secondary structural elements.
• Wealth of experimental information, difficult to
  grasp.
• Folding pathways were embraced to explain
  observations.

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Thermal unfolding
Creighton, Proteins, structure and molecular
properties, Freeman, New York, 1993
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Theory of protein folding (2)

• Levinthal paradox proteins fold to slow by
  undirected random searching possible
  conformations ? Kinetic problem.
• Late 1980s New View of protein folding
• proteins energy surface.
• Folding occurs through an ensemble of structures
  rather through only a few uniquely defined
  structural intermediates ? Statistical
  description of energy landscape.
• Folding funnel.

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Classical folding mechanisms
Fersht, Structure and function in protein
science, Freeman, New York, 1999
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Funnelscape for fast folding protein
Chan and Dill, Proteins, 30, 2-33 (1998)
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Protein folding versus condensation of atomic
clusters
solid
liquid
gas
native state (100)
random globule (1026)
random coil (1044)
Dobson et al., Angew. Chem. Int. Ed. 37, 868-893
(1998)