Why those dihedral angles? Why helices? Strands? & What are Ramachandran plots plotting? (Revenge?)

A Ramachandran Plot shows the backbone angles taken by atoms in a peptide or protein - usually colored heat-map style to show you the most common and least common angles.Despite being kinda opposites, the two amino acid Ramachandran outlaws (proline & glycine) often work as partners in crime (or more like partners in cool chemistry). They’re often found together in sharp turns, where Pro helps reinforce the kink & G’s small enough to squeeze in. 
All protein backbones have limited flexibility because the peptide bonds linking them together get stabilized by resonance (electron delocalization where “extra” electrons are shared among more than just 2 atoms), which can only happen if Ca, N, & O are in the same plane, so you end up with a chain of planes where you can only rotate at certain places in the backbone (C-Cα (psi) & Cα-N (phi)). And even those rotations are restricted by steric hindrance (you can’t have atoms colliding with one another so bulky side chains restrict movement more). bit.ly/aminoaci...  
But even that twisting is restricted, depending on the nature of the side chain because of “steric hindrance” - that’s basically a fancy way of saying 2 things can’t be in the same place at once (even if they’re super super small). Bulky things need more space, leaving them with fewer available ways to move without hitting something - like the atoms of the peptide backbone. So bulkier side chain → more steric hindrance 
 
The thing about glycine is that its side chain is just an H - which is pretty damn small - movement-wise it’s like there’s barely anything there at all! As a result glycine has very low steric hindrance, so glycine residues are very flexible (remember residue’s just what we call an amino when it’s in a peptide chain so has lost that water-equivalent (I don’t mean to harp on about this I was just confused about it for a really long time but embarrassed to ask!)) 
 
So glycine’s smallness lets its backbone take on awkward angles that would be major no-nos for other amino acids. You can see this if you look at a Ramachandran Plot. When we’re solving a crystal structure (more later) we often check that the angles are geometrically solid & one of the things you’ll see in the “report card” for a structural model is “Ramachandran outliers” - atoms in the model that have suspicious angles. Usually it’ll be reported as “non-glycine,” “non-proline” Ramachandran outliers - basically glycine can “break the normal rules” because it’s so small (its side chain’s just an H) so it’s ok to find it at weird angles. Proline can also break the rules, but instead of being able to move lots more ways, like glycine, it just has “different rules” - it’s restricted to different angles. Here’s the link for the paper in the figure: doi.org/10.100...  
Glycine’s “loosey-goosey-ness” makes it good for flexible regions of proteins BUT bad for places you need strong structure. So it’s often found in sharp turns leading into or out of more orderly structures like helices & sheets. 
 
It’s typically only found in small amounts in protein, though it is the most abundant in the weird triple-helices of the protein collagen that helps make our skin stretchy but sturdy. But it’s found a lot of other places too. In its free form it acts as a neurotransmitter - a chemical messenger relaying news throughout the brain. And it is a member of the antioxidant tripeptide glutathione, which helps control oxidation status in our bodies.
 
The other Ramachandran weirdo is Proline. Proline’s backbone N can’t form them H-bonds. Normally, the generic backbone offers 2 locations for H bonding. The carbonyl (C=O) provides an H-bond acceptor in the form of the O and the amino group provides an H-bond donor in the form of the N-H. Therefore, backbones can interact through H-bonds to give a protein its “secondary structure” (common “structural motifs” like helixes, sheets, etc) bit.ly/insulind...  
 
BUT Proline’s N doesn’t have this H because it’s “been replaced” by a bond to side chain. So it can’t act as a donor. Thus, it doesn’t want to form α-helixes, and if it’s in them it’ll make them kinky. Proline can also make other places kinky because its side chain contortion “locks” the N-Ca bond in place, leading to limited backbone flexibility - even limited-er than usual!  
 
All protein backbones have limited flexibility because the peptide bonds linking them together get stabilized by resonance (electron delocalization where “extra” electrons are shared among more than just 2 atoms), which can only happen if Ca, N, & O are in the same plane, so you end up with a chain of planes where you can only rotate at certain places in the backbone (C-Cα (psi) & Cα-N (phi)). And even those rotations are restricted by steric hindrance (you can’t have atoms colliding with one another so bulky side chains restrict movement more). bit.ly/aminoaci...  
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[@thebumblingbiochemist]

More on peptide bonds & secondary structure: bit.ly/proteinstructure ; TH-cam: th-cam.com/video/FFAhrp3EEoM/w-d-xo.html  
resources: Ramachandran tutorial: bioinformatics.org/molvis/phipsi/ & tinyurl.com/RamachandranPrinciple
& Tutorial:Ramachandran Plot Inspection - Proteopedia, life in 3D proteopedia.org/w/Tutorial:Ramachandran_Plot_Inspection
bioinformatics.org/molvis/phipsi/?fbclid=IwAR2O2hRdLXtazAqPStaiUAQueCvrWuWGLOcJ7uW32_0m_dMtmBVVwlFw33s
proteopedia.org/w/Tutorial:Ramachandran_Plot_Inspection
proteopedia.org/w/Ramachandran_Plot
posts on proteins and amino acids: thebumblingbiochemist.com/lets-talk-science/amino-acids/   
  
TH-cam channel on amino acids: th-cam.com/play/PLUWsCDtjESrFQoCEsEmZX6NxnwlHzjHZ6.html  
                             
more about all sorts of things: #365DaysOfScience All (with topics listed) 👉 bit.ly/2OllAB0 or search blog: thebumblingbiochemist.com                                      
                                        
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