> See also: > - [[Proteins]] > - [[Protein Structure]] > - [[Amino Acids]] # Protein Conformational Changes For a protein to fold properly, its backbone and side chains must adapt conformations that maximize favorable interactions Levinthal’s paradox states that it would be impossible for a protein to attempt every single conformation during its folding process (would take gt;10^{77}$ years), and yet, folding takes place within seconds, likely in a stepwise manner ![[Pasted image 20240226120132.png|300]] it is instead theorized that proteins first fold locally with nearby residues Surprisingly, the properly-folded shape of most proteins is only -3 to -7 kcal/mol more favorable than other intermediate states - Many diseases are related to protein misfolding ## The Hydrophobic Core > See also: > [[Intermolecular Forces#The Hydrophobic Effect|The Hydrophobic Effect]] In aqueous solutions (polar), proteins with a large amount of nonpolar side groups will tend to internalize the nonpolar residues - Leads to higher stability than proteins composed of only polar residues Polar groups are able to H-bond with water, meaning that a smaller free energy would be gained This core can be composed of nonpolar-coated alpha helices ## Conformational Impact of H-Bonds nonpolar residues play a large role in folding, but lack the “directionality” of polar residues a few kcals of energy stability is lost for each unbound H-bond