Bi1_2009_Lecture23_full

Critical threshold stability gf gf protein stability

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Unformatted text preview: ons are now acceptable. (critical threshold stability) Gf Gf “Protein stability promotes evolvability.” JD Bloom, ST Labthavikul, CR Otey, and FH Arnold. Proc Natl Acad Sci, 103:5869-5874 (2006). Evaluating stability Two state unfolding transition N <--> D Monitor property of folded protein as function of increasing temperature Transition midpoint (Tm) Shows that class I MHC molecules require bound peptide for thermal stability “Family” shuffling experiment From Frances Arnold’s website: www.che.caltech.edu/groups/fha From Frances Arnold’s website: www.che.caltech.edu/groups/fha Protein Library Design multiple sequences 1 structure Sequence Space Structure Space Mayo lab, Caltech Protein Fold Prediction versus Protein Design 1 sequence 1 structure Sequence Space Structure Space Mayo lab, Caltech Computational Protein Design: Rationale by the Numbers Combinatorial Explosion 1 protein p residues 20 amino acid types 20 p sequences Residues 18 37 42 59 Sequences 1023 1048 1054 1077 Mass Baseball Earth Sun Universe Mayo lab, Caltech Methods Atom-Based Forcefields Rotamer...
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