Protein_Folding - Protein Folding BIBC 100 The Folding...

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Protein Folding BIBC 100
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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 earth/universe
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Levinthal’s 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.
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Second Genetic Code : Sequence Structure Folding Design (reverse folding ) Computer Algorithm Input Output Folding Sequence Structure Design Structure Sequence
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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
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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
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Physical Forces
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