Lectures 6 & 7 -Protein_Folding

Lectures 6 & 7 -Protein_Folding - Protein Folding...

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Unformatted text preview: Protein Folding BIBC 100 The Folding Problem How Proteins Fold? Consider a protein with 100 a.a. 10 100 possible conformations (avg. of 10 conformations/a.a.) If it converts from one conformation to another in ~10-13 sec then the avg. time to sample all conformations would be 10 77 years or 10 85 seconds Cosmic Term: longer than the life of Levinthals Paradox However, in vivo, proteins fold in 10-1- 10 3 seconds, a mismatch of >98 orders of magnitude Conclusion: Folding is not random deterministic (directed) Native State (folded state) U nique (action) S table (energy) A ccessible (kinetics) U.S.A. Second Genetic Code : Sequence Structure Folding Design (reverse folding ) Computer Algorithm Input Output Folding Sequence Structure Design Structure Sequence Importance? 1. Too many sequences and still few structures (10 5 10 6 , genome) (~10 5 ) Understanding seq.-struct. relation requires solving: 2. Biotechnology unleashed power Design : drugs, hormones, sensors, processes (photosynthesis), imagine Too many structures or The Folding Problem Characteristics of Folded State Tight packing compact Sequence determined/environment modulated (N-P) Search Space Families and symmetry Each sequence unique structure Native state is thermodynamically stable (lowest energy) USA Dogma Characteristics of Folded State Tight packing compact Sequence determined/environment modulated (N-P) Search Space Families and symmetry Each sequence unique structure Native state is thermodynamically stable (lowest energy) USA Dogma Physics of Folding Enthalpy drives towards this HB interactions H bonding Ionic interactions Free Energy is the Difference Folded state is more stable Entropy drives towards this HB exposed Steps of Folding Unfolded bury core 2 o Molten globule 3 o 4 o protein HB aa (loose 3 o ) (breathing) < ms Up to 1s Energy Funnel for Folding Multiple folding pathways can occur Model this with energy funnel Physical Forces...
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Lectures 6 & 7 -Protein_Folding - Protein Folding...

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