The Energetics of Protein Folding and Unfolding: A Detailed Explanation

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SUMMARY

The discussion centers on the energetics of protein folding and unfolding, specifically analyzing the signs of Gibbs free energy (delta G) and entropy (delta S) during these processes. At low temperatures, delta G is positive, favoring protein folding, while at high temperatures, delta G becomes negative, leading to unfolding due to increased entropy. The main interactions disrupted during unfolding include hydrogen bonds, disulfide bonds, salt bridges, and hydrophobic interactions. The spontaneous nature of folding is driven by the amino acid sequence and is influenced by Van der Waals forces and entropic contributions.

PREREQUISITES
  • Understanding of Gibbs free energy and its components (delta G, delta H, delta S)
  • Knowledge of protein structure and the role of amino acids
  • Familiarity with thermodynamics principles in biochemistry
  • Awareness of molecular interactions (hydrogen bonds, disulfide bonds, salt bridges)
NEXT STEPS
  • Study the role of Van der Waals forces in protein stability
  • Learn about the thermodynamics of protein folding using the Gibbs free energy equation
  • Explore the effects of temperature and pH on protein structure
  • Investigate methods for analyzing protein folding pathways, such as molecular dynamics simulations
USEFUL FOR

Biochemists, molecular biologists, and students studying protein chemistry who seek to deepen their understanding of protein folding mechanisms and thermodynamic principles.

PremedBeauty
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Desperate Need of Help!

I've done my homework (except one problem) and I want to make sure I am correct?

1. What is the sign (delta G) for the folding process? Unfolding? How do you know?
-(delta G) at low temp is positive and equilibrium will favor protein folding. At high temperature, delta G is negative and unfolding occurs because strong increase of change of entropy that lowers Gibbs free energy.

2. What is the sign for (delta S) “ “
-Unfolding (delta S) is positive and folding is negative because breaking of favorable interactions holding the folded protein will need input of energy , and delta H will increase also. When temperature increases, randomness increases and denaturation occurs at high temperature. Folding is in relation to decrease in randomness (at low temperature) and becomes more ordered.
3. What will contribution of delta S to the free energy change be positive or negative? What does this mean?

4. What are the main bonds and interactions that must be broken or disrupted is a folded polypetide is to be unfolded? Why does heat or ph cause unfolding?
-H-bonds, disulphide, salt bridges, and hydrophobic interactions are disrupted. If heat is added, vibrational modes in the molecule will be excited and will disrupt hydrophobic interactions and dipole-dipole interactions and denature protein. If ph were to change, the protonation state of amino and carboxyal groups change and ionic bonds in the proteins disrupt and disrupts salt-bridges.
 
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Biochemistry is not my area, although I do find it fascinating. Nevertheless, I found this. http://en.wikipedia.org/wiki/Protein_folding
The essential fact of folding, however, remains that the amino acid sequence of each protein contains the information that specifies both the native structure and the pathway to attain that state: Folding is a spontaneous process. The passage of the folded state is mainly guided by Van der Waals forces and entropic contributions to the Gibbs free energy: an increase in entropy is achieved by moving the hydrophobic parts of the protein inwards, and the hydrophilic ones outwards. This endows surrounding water molecules with more degrees of freedom. During the folding process, the number of hydrogen bonds does not change appreciably, because for every internal hydrogen bond in the protein, a hydrogen bond of the unfolded protein with the aqueous medium has to be broken.
If a process if spontaneous, what is the sign on Gibbs free energy?

http://ocw.mit.edu/NR/rdonlyres/Health-Sciences-and-Technology/HST-508Fall-2005/2258C576-52A7-4492-A812-896F02EF46B6/0/lecture_st2.pdf pdf file.

http://www.cryst.bbk.ac.uk/PPS2/projects/day/TDayDiss/index.html

http://www.chembio.uoguelph.ca/educmat/phy456/456lec02.htm
 
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Thank you very much!

Can you interpret question 3 for me?:
3. What will contribution of delta S (entropy) to the free energy change be positive or negative?
 

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