HHMI meeting, FOLDING

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PROTEIN PHYSICS LECTURE 25
PROTEINS AT ACTION
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Preferential binding of TS RIGID enzyme
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Preferential binding of TS RIGID enzyme

• F k1x1 - k2x2 Ei (ki
  /2)(xi)2 F2/(2ki )
• Hookes 2-nd Newtons Energy
  is concentrated
• laws
  in the softer body.
• 
  Effective catalysis when
• 
  substrate is softer than protein
• Kinetic energy cannot be stored for catalysis
• Friction stops a molecule within
• picoseconds
• m(dv/dt) -(3?D?)v Stokes law
• D diameter m D3 mass ? viscosity
• tkinet ? 10-13 sec ? (D/nm)2 in water

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Catalysis stabilization of the transition
state Theory Pauling Holden Experimental
verification Fersht
______
__________
P
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Different folds with the same active site the
same biochemical function
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Similar folds with different active sites
different biochemical function
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Standard positions of active sites in protein
folds
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MOTIONS
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Double sieve movement of substrate from one
active site to another
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Movement in two-domain enzyme One conformation
for binding (and release), another for catalysis
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Two-domain dehydrogenases Universal NAD-binding
domain Individual substrate-binding domain
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Movement in quaternary structure Hemoglobin vs.
myoglobin
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Myosin Actin
Mechanochemical cycle
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SUMMARY
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PROTEIN PHYSICS

• Interactions
• Structures
• Selection
• States transitions

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• Intermediates nuclei
• Structure prediction bioinformatics
• Protein engineering design
• Functioning