Lecture 18 -Protein Design and Engineering

Asn asp ser asp helix protein stability 4

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ASN ASP, SER ASP) Helix:
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Protein Stability 4. Hydrophobicity in the core (cavity) -Barnase (bacterial RNAse-110 a.a.) -structure by both x-ray and NMR -introducing cavities in the core by mutations such as Ile Val or Phe Leu Cavity for a CH2 Stability by 1kcal/mol -More delicate design -Needs structure
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Agonist of the erythropoietin receptor identified from peptide libraries
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Prediction of Structure From Sequence Empirical – in progress ~75% successful-at best (62-65%). For the membrane- embedded domains of membrane proteins up to 90% Essence: Pattern Recognition Key: Evolutionary Information Sequence homology implies similarity in structure and function By inference/By Anaysis Data bases (2007 >500,000 seq., >45,000 Structures Information Prediction Example: Homologous proteins Conserved Core Variable Loop
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Secondary Structure Prediction for 3-Model Predict: α, β, loop, β-turn Predict: membrane-spanning α-helix Predict: Amphipatic structures α β Prediction of the folded structure of tryptophan synthetase, and the catalytic subunit of c-AMP dependent protein kinase
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Chou & Fassman (1974) Frequency of occurrence of a given a.a. in α, β, and loops in all protein structures in the
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  • Spring '07
  • Nehring
  • protein stability, Protein Stability Cont…, Evolutionary Information, hypervariable loop

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