Atreyi Saha, Amy Camp January 30, 2014 Unit 1: Lipids and Membranes - Protein Folding and Secondary

Structure 1. Protein folding is spontaneous (continued)

Equation: (Delta G) = DeltaH - TDeltaS o Delta G = Change in free energy (useful and usable energy) negative delta g is spontaneous o Delta H = Change in enthalpy (heat) negative delta H means delta H is released o Delta S = Change in entropy (disorder) positive means more disorder Membrane assembly is also spontaneous

o Phospholipid entropy = Delta S is greater than zero thus pushing the delta G to be more positive (unfavorable) The phospholipids themselves are less disordered and more ordered because they are assembling into a bilayer instead of freely floating around

o Water entropy = Delta S is less than zero thus pushing delta G toward a more negative direction (favorable) Around free floating phospholipids, water forms cages around the hydrophobic fatty acid tails When the phospholipids are in a bilayer, the hydrophobic interactions are minimized and water does not form cages anymore The increase of entropy in water has a huge impact that counteracts the decrease of entropy due to phospholipids reordering o Non-Covalent interactions Van Der Waals between C-C and C-H bonds (fleeting dipole) - the summation of these is significant Van der waals occurs because the fatty acids are nonpolar

The water entropy effect combined with the large value for a negative delta H due to the summation of the van der waals interactions among fatty acids drives delta G negative meaning in a favorable direction. Protein Folding is spontaneous o Unfolded protein - more disorder because more open and able to interact to surroundings Delta S = positive Delta G = negative o Folded protein - more ordered that is why it drives the delta G toward a more positive direction which is unfavorable Delta G = positive Delta S = negative

Entropy of the peptide chain conformation: the protein goes from an unfolded spaghetti loose type structure to a folded structure. Thus, it becoming more ordered thereby driving delta G in an unfavorable direction. BUT WAIR, PROTEINS ALWAYS FOLD SO THERE MUST BE A CATCH/OTHER FACTORS TO TAKE INTO ACCOUNT!!!! o The process of protein folding occurs in an aqueous environment meaning that we have to take water into account - meaning how the R groups of the peptide chain are interacting with water

The answer is B because the hydrophobic R groups are able to limit their interaction with water. No cages are formed by water so water is happy because of the increase in entropy. By adopting this conformation, the polar R groups can interact with water and the non polar R groups are hidden away from water. This separation due to affinity for water is highly desirable. Thus, the folding of the protein/confirmation is driven largely by the entropy of the water. Side Note: Not all non polar R groups are in the center but most of them are - this goes back to the point that every protein is different.

This diagram shows how the increase in entropy of the water pushes delta G down in a favorable way. Also, not all proteins are the same. Every protein is different

and this is why the size of the arrows may be changing ever so slightly for individual proteins. But we are still not at the point where protein folding is spontaneous, time to consider other factors! o Noncovalent bonds in protein folding (Consider delta H) These interactions/intermolecular forces are not happening when the protein is unfolded Examples of interactions Electrostatic Interactions - Happen between Positive/Negative R groups Van Der Waals - occurs between the nonpolar amino acids - C-C and C-H bonds have fleeting dipole moments Hydrogen bonding - this is a weaker version of electrostatic interactions that occurs between atoms that are partially negatively/positively charged Look for atoms that can attract with other atoms in the back bone Electrostatic interactions and hydrogen bonding occurs only between polar/charged amino acid groups (Acidic and Basic amino acids) Amino acids that are uncharged and nonpolar cannot hydrogen bond or have electrostatic interactions Instead, they have van der waals interactions Small electron clouds come together creating fleeting dipole moments The summation of the van der waals forces leads to a significant influence o Noncovalent bonds may be weaker and more transient than covalent bonds but each interaction is associated with a small delta H value Each individual bond has its own delta H value and these add up Since there are MANY of these interactions, the summation of these is significant enough to produce a sizable value for delta H The negative delta H value is favorable and drives delta G down which is also favorable!

This figure shows the various non covalent interactions that produce a favorable value for delta H and thereby make delta G more favorable.

Now, we have all of the pieces of the puzzle. This figure shows how protein folding is spontaneous!

Protein folding goal: we want the most negative value for delta G possible (delta G minimized) o Two favorable forces that counteract the decrease in entropy for both protein folding and membrane assembly: Hydrophobic Effect (Water entropy counteracts) Noncovalent interactions (Makes delta H more negative) We need BOTH favorable factors to have proteins fold, not just ONE favorable factor by itself The Protein Folding Problem

Transcription (RNA Polymerase involved here) ---> Translation o Protein primary sequence is from N to C terminus o The primary sequence of the protein does not give any information as to what the tertiary structure will be that it folds into o We understand that protein folding is spontaneous, but we cannot tell how it folds

Secondary structure of proteins = alpha helices and beta sheets o secondary structures are result of hydrogen bonding between the N-H groups and the C=O groups in the peptide backbone o R groups are not involved in the formation of secondary structures

o Hydrogen bonds form at the rungs of the helix and these hydrogen bonds run parallel to the alpha helix - they hold the helix together (bond between O of C=O and H of N-H)

This is the alpha helix.

N terminus is up because nitrogen is to the left of the alpha carbon and C terminus is down. Every turn of the alpha helix is four amino acids away n, n+1...n+4 that is where the hydrogen bond occurs. o R groups stick out in the alpha helix as seen below