BIOT 226 |
| We develop a statistical mechanical theory for the equilibrium folding of helix bundle proteins and peptoids. A longstanding problem has been how to treat local interactions in chain molecules, such as those that dominate helix-coil processes, together with non-local interactions, such as those that dominate collapse processes. We use a dynamic programming algorithm to efficiently compute the partition function for a 3-helix bundle homopolymer, modeled on a cubic lattice. We determine energy parameters to match experimental thermodynamic parameters and denaturation curves. Our energy function is based on three parameters, a helix interaction energy, a hydrophobic contact term and a three-body interaction energy. A three-body interaction term is necessary to capture calorimetric two-state cooperativity. We find a helix to hydrophobic interaction energy ratio of 1.3:1. Interestingly, the model predicts the balance of forces that explains why two-helix bundles are not observed in proteins, and yet are stable states of peptoids. |
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Biophysical and Biomolecular Symposium: Protein Folding and Posttranslational Modification
3:00 PM-5:30 PM, Wednesday, 13 September 2006 Hilton San Francisco -- Imperial B Ballroom, Oral
Division of Biochemical Technology |