1 / 30

CMSE SEMINAR

CMSE SEMINAR. Protein Folding mechanisms By Sefer Baday. OUTLINE. Proteins Protein Folding Forces Driving Folding Energy landscape The folding mechanism models Conclusion. Some Facts about Proteins. Composed of amino acids.

whiting
Download Presentation

CMSE SEMINAR

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. CMSE SEMINAR Protein Folding mechanisms By Sefer Baday

  2. OUTLINE • Proteins • Protein Folding • Forces Driving Folding • Energy landscape • The folding mechanism models • Conclusion

  3. Some Facts about Proteins Composed of amino acids. Each sequence fold in unique structure-native structure Proteins are functional only in their native states Folding is reversibe unfolding or re-folding is possible Modest changes in the environment can cause structural changes in the protein,thus affecting its function

  4. SECONDARY STRUCTURE (helices, strands) PRIMARY STRUCTURE (amino acid sequence) VHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH TERTIARY STRUCTURE (fold) QUATERNARY STRUCTURE (oligomers) Protein structure hierarchical levels

  5. Random Coil Native conformation What is Protein Folding ? • Protein folding is the process by which a protein assumes its functional shape or conformation.

  6. Why is the “Protein Folding” so important • Most of the proteins should fold in order to function • Misfolding cause some diseases. • Cystic Fibrosis ,affects lungs and digestive system and cause early death • Alzheimers’s and Parkinson's disease • It may help us to understand the structure of proteins which has not been known

  7. LEVINTHAL PARADOX • Let have Protein composed of 100 amino acids. • Assume that each amino acid has only 3 possible conformations. • Total number of conformations = 3100 ~= 5x1047 . • If 100 psec (10-10 sec) were required to convert from a conformation to another one, a random search of all conformations would require 5x1047x 10-10 sec = 1.6 x 1030 years. However, folding of proteins takesplace in msec to sec order.

  8. Forces that stabilize protein structure • Interactions between atoms within the protein chain • Interactions between the protein and the solvent

  9. Electrostatic Interactions • Interaction of charged side chain with the opposide charged side chain.

  10. Hydrogen Bonds • Noncovalent bond • Energy:10-40 kJ/ mol • Strength varies with angle of hydrogen bond interaciton.

  11. r0 Van der waals radii of common atoms (nm): H 0.1 nm C 0.17 nm N 0.15 nm O 0.14 nm P 0.19 nm S 0.185 nm Van der Waals potential Van der Waals Force r r0 van der Waals forces • Between all atoms • Approximately 1kj/mol

  12. Average Strength of Interactions

  13. The Hydrophobic Interaction • Hydrophobic means afraid of water • Hydrophobic residues are buried in while hyrophilic residues stay outside.

  14. Hydrogen Bonds

  15. The kinetic Theory of Protein Folding • Folding proceeds through a definite series ofsteps or a Pathway. • A protein does not try out all possiblerotations of conformational angles, but only enough to find the pathway.

  16. Energy Landscape

  17. Energy Landscape

  18. Molten Globule

  19. The average separation in the sequence between residues that are in contact with each other in native structure Contact Order

  20. Phi Value Analysis • Experimental method to study of the structure of the transition state • Using mutations as a structural report • Phi=1, transition state has native like structure • Phi=0, transition state has denatured like structure

  21. unfolded state Transition state native state The Framework Model • Local interactions are main determinants of protein structures

  22. unfolded state collapse native state Hydrophobic Collapse • Hydrophobic core forms first.

  23. Hydrophobic Collapse • Formation of hydrophobic globule may hinder the reorganization of both side chains and whole protein

  24. unfolded state formation of a nucleus native state Nucleation Model • Unites hydrophobic collapse and frame work model

  25. Nucleation Model • Substantial expulsion of water from the burial of non polar surfaces • Good correlation between decrease in hyrodynamic volume and increase in secondary structure

  26. Unfolding simulation of Ci2

  27. The folding Pathways of Barnase

  28. Conclusions Non local interactions( Hydrophobic effect and van der waals ) are needed to bring protein into a globular conformation. Chemically specific interactions( hydrogen bonds, electorstatic interactions) determine the fine detail of the protein structure

  29. Conclusions • The folding process is hierarchical • Native topology affects the folding mechanism. • Nucleation method explains folding mechanism better than framework and hydrophobic collapse methods.

  30. THANK YOU  QUESTIONS ???

More Related