Protein Folding, Bridging Lattice Models and Reality

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Protein Folding, Bridging Lattice Models and
Reality

• Skorobogatiy Maksim, Ned Wingreen, Chao Tang
• NEC, Princeton, NJ

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The Protein Folding Problem
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A Reductionists Approach
Real Problem
Simple Model
General Features From Simple Models
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Physical Interactions
Van der Waals interaction Electrostatic
interaction Hydrogen bonding Hydrophobic
interaction
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Essentials for a Minimal Model of Protein
Folding

• Self-avoiding polymer
• At least two different types of monomers
• Short range contact interaction

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HP Model on a Lattice (Lau, Chan, Dill)
Sequence s Structure r
2D
3D
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Designability of Structures
A structure S is designable by a sequence s if
S is the unique ground state of s
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Designability Histogram
Number of structures
Number of sequences designing a structure
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Most Designable Structures
a Helix
b Strand
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Characterizing Highly Designable Structures
What are the geometric properties which make
These structures special ?
112222221101221122101122110122112210
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Real Proteins
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Implementation of Realistic Geometries
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Thermodynamics
FE-TS NbbEbbNwwEwwNwrEwrNwbEwb- -TSchain-TSso
lution Schain is simulated by MD or
MC SsolutionNwwSwwNwrSwrNwbSwb NwwN0-Nwr-Nwb
F-N0(Eww-T Sww) NbbEbb Nwr((Ewr-
Eww)-T(Swr-Sww)) Nwb((Ewb- Eww)-T(Swb-Sww))-TSch
ain
F-F0 NbbEbb NwrEwr NwbEwb- TSchain
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Compact Structures Space
F-F0 -NbbEbb NwrEwr- NwbEwb- TSchain
Ebb
Ebb lt 0 Ewr gt 0 Ewb lt 0
Ewb
Ewr
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Spanning the Phase-Space
Globular
a Helical
b Strand Globular
Real protein like
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Coarse-Graining the Structures
110010111110000010100...
Surface to Bulk Transition Rate
Surface to Core Ratio
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Rate of Surface to Bulk Transitions