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Outline:
• Introduction: What is Protein?• Protein Folding
• Native State• Mechanism of Folding• Energy Landscape• Kinetic Trap• Fast Folding
• H-P Lattice Model• Our Sample Protein and Its Native State• Summary
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• Role of Proteins in Organism:– Catalyzing Biochemical Reactions,– Maintaining Cells Shape,– Cell Signaling,– Immune Responses,– Cell Adhesion,– Cell Cycling,– …
• Functional Size of Protein is between 40 to 50 Amino Acid up to a Chain with Several Thousand Residue.
• Human Body Makes at least 50,000 Different Type of Proteins with Different Functionality.
What Is Protein?
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Structure of Protein
1- Primary Structure: Sequence of Amino Acids
2- Secondary Structure: Repeating local structure stabilized
by hydrogen bonds
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Alpha-Helices
Protein Folding
• Native State: A unique completely determined folded state.
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• Protein Folding: Process of collapsing of protein to the folded structure.
• Folding to the correct state is essential for function correctly.
• Mis-folding, usually results in inactive proteins, might cuase several diseases like Alzheimer, etc.
Protein Folding
• Protein Folding is Dominated by Hydrophobic Residues.
• Hydrophobic: Non-polar, Make Cluster in Polar Solvents.
• Hydrophilic: Polar, Dissolve More Readily in Polar Solvents.
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Protein Tries to Maximize the Contacts Between Its Hydrophobic Residues.
Protein Folding
How can Protein Find Its Native State Correctly?
How Does It Fold to Its Native State?
Energy Landscape
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Protein FoldingMistakes are mainly because of:
• Kinetic Traps,• Thermal Motions,• Retrying the Earlier Conformation,• Etc.
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These effects could either misfold the protein or delay the protein folding process significantly.
Protein FoldingUnfolded Protein
Fast Collapse to a Compact Form with Hydrophobic Core.
Internal Reformations
Native State
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Method
Sequence
Using Self Avoiding Random Walk
Generate Many Conformations.
Count Number of HH Contacts in
Each Conformation.
Find the Conformation with the Greatest
Number of HH Contacts.
Native State
Start
A
A
End
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Summary
• Protein folding is a complex process.• The folding process is dominated by
Hydrophobic interactions.• At Native state, Hydrophobic contacts are
maximized.• Toward Native state, a protein makes many
mistakes.• HP Lattice model could describe general
behavior of folding process and Native state.
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