1. PROTEIN FOLDING: H-P Lattice Model 1

2. 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 2

3. 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? 3

4. Structure of Protein 1- Primary Structure: Sequence of Amino Acids 2- Secondary Structure: Repeating local structure stabilized by hydrogen bonds 4 Alpha-Helices

5. Structure of Protein 3- Folded Structure: 5

6. Protein Folding Native State: A unique completely determined folded state. 6 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.

7. 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. 7 Protein Tries to Maximize the Contacts Between Its Hydrophobic Residues.

8. Protein Folding At Native State: CONTACT BETWEEN HYDROPHOBIC MOLECULES IS MAXIMIZED. 8

9. Protein Folding How can Protein Find Its Native State Correctly? How Does It Fold to Its Native State? Energy Landscape 9

10. Protein Folding What is the Systematic Way of Finding Native State? Kinetic Traps!!! 10

11. Protein Folding Mistakes are mainly because of: Kinetic Traps, Thermal Motions, Retrying the Earlier Conformation, Etc. 11 These effects could either misfold the protein or delay the protein folding process significantly.

12. Protein Folding Unfolded Protein Fast Collapse to a Compact Form with Hydrophobic Core. Internal Reformations Native State 12

13. HP Lattice Model 13

14. Our Problem We Develop a Code to Find the Native State of Protein in HP Lattice Model. 14

15. 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 15

16. Results H P 16

17. 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. 17