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The second law of thermodynamics dictates that the sum of entropy of the universe is always increasing. Is the process of protein folding a spontaneous process which is increasing the entropy? Is this why it can be called thermodynamically favourable? Or is there something else I am forgetting..

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What determines whether a process is spontaneous or not, is the change in free energy, not the increase of entropy. Entropy is one important factor, as is enthalpy. Entropy in this case is not increasing since the system is becoming more organized, however,enthalpy is greatly favoured since protein folding creates many Hydrogen bonds between its polar aminoacid fragments and surrounding water and also many hydrophobic interactions between their non-polar aminoacids constituents. Take a look at this page to have a better understanding about protein folding thermodynamics (introductory text, though it´s a good starting point). http://www.chembio.uoguelph.ca/educmat/phy456/456lec02.htm

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  • $\begingroup$ You're ignoring the hydrophobic effect, which is usually considered a major driver of protein folding. Packing the hydrophobic amino acids inside the protein core during folding does increase the entropy of the water around the protein. $\endgroup$ Jul 19, 2017 at 13:18
  • $\begingroup$ To be precise, for a process to be spontaneous, the entropy of the system can increase or decrease, but the entropy of the universe must increase. To say that a process decreases the free energy of a system is exactly equivalent to saying that it increases the entropy of the entire universe. $\endgroup$ Jul 19, 2017 at 13:19
  • $\begingroup$ @NicolauSakerNeto you are absolutely correct! When I said entropy decreased I meant the system entropy. $\endgroup$ Jul 19, 2017 at 20:33

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