Proteins (BIOC1001)

Proteins have many roles to play in nature. This roles fall into 4 major functional groups: (even though every role involves a binding event), (enzymes speed up reactions that turn into metabolites), (receptors that bind changing conformation and triggering internal response) and (such as collagen in matrix or keratin in your hair and nails).

R groups can also be since they also have pKa which depends on and of amino acid. In proteins, the of the and groups can be ignored since they cancel each other out at N and C terminus. Thus, only pKa's influence of protein, which is, therefore, dependent.

Amino acids with hydrocarbon side-chains are non-polar and thus . The higher the aliphatic complexity the more and, therefore, tend to be in the of the protein sequestered away from the solvent. The most hydrophobic amino acids are and , the latter having due to the 2 chiral centers, whereas the least complex, , tends to be in due to imparted structural flexibility. There are, however, a few exceptions where you can find aliphatic side-chains on the protein surface, for instance if it binds to hydrophobic substrate/ligand or other hydrophobic protein.

Sulfur containing side-chains are () but is extremely reactive (sometimes can be found in sites), polarisable and can loose H+ to become S- ion. It is also responsible for the formation of (covalent), which give proteins and conformational rigidity), especially found in proteins required to be or to stabilize folding of polypeptides.

is a special amino acid whose side-chain contains a , like Tyrosine, Phenilalanine and Tryptophan. Nevertheless, it is unique in that it has no free group to form H-bond with group further down the chain. Thus, it halts formation and, hence, is called . Furthermore, whereas normally configuration of peptide bonds is favored (alpha-carbon substituents as far apart as possible, facing sides), in amide bonds involving there is higher probability of forming configuration (facing side), giving rise to strange configurations.

The peptide bond is (no rotation) but the C-C and C-N bonds on either side are , thus determining shape of polypeptide which is key for complex protein structure. The torsion angles around C-C and C-N are the and angles, respectively. Rotation is determined by nature of groups. plotted allowed and angles (the degrees of freedom of bonds in proteins) according to (physical size of atoms/groups of atoms limits possible torsion angles). If all and angles are the same, peptide assumes repeated structure, such as a- or B-.

Chemical reactivity of a polypeptide chain is determined by the nature and location of the bonds ( structure), the carbonyl and amide N ( structure) and the groups attached to the alpha-C. The combination of these re reactivities determines folding and folded structure of proteins. Although proteins are linear polymers, they don´t form random conformations. Most are with core and the amino acid chain takes up conformations with regular patterns of torsion angles and . The resultant regular segments make up the structure.

Secondary structures are formed by H-bonds between N and carbonyl of peptide groups in polypeptide chains. Hence, not surprisingly, the 2 most common configurations, and , are the ones which H-bonding. Alpha-helices are formed by repeated pattern of H-bonding between carbonyl and close N residues further down the same chain. All polar and carbonyl groups are H-bonded except N and last . have no fixed pattern since the H-bonds occur between distant groups. However, these are always present (no free polar amide or carbonyl groups), apart from the strands.

The structure of a protein is the final folded polypeptide chain held together by mostly interactions in its most structure. The interaction between groups and between these and dictates the structure. The fact that those interactions are relatively , and therefore break and reform easily, allows for structural which is key to protein . Flexible regions are often (long stretches of amino acids between secondary structure elements) that protrude into the solvent being involved in and, since they don´t contribute to , are more prone to which provides a mechanism for molecular . Apart from the functional regions, often there are inflexible/rigid regions which can require additional stabilization provided by: 1- (covalent bonds between residues); 2-coordinate covalent bonds with (mainly Ca2+ and Zn2+, distinct from metal ions in sites) and 3-stabilization by binding (required by some proteins to exhibit activity and for stability). Hence, tertiary structure can exhibit various distinct with particular shapes and functions. (phosphorylation, glycolisation, ubiquitination...) also change an stabilize tertiary structure, as well as , whether forming an that exerts pressure providing stability or the molecules trapped the protein which can be important for structure and activity.

The effect, the clustering of hydrophobic side-chains in the protein's , is the major driving force behind . Non-polar groups are sequestered away from the solvent to contact area with because, as they cannot form , they would disrupt H-bonded network of water. This also brings polarisable groups together allowing interactions. Hence, generally polar side-chains tend to be on the of the protein whereas ones tend to be on the core. Nevertheless, not only polar residues, as well as water, can be dragged away (or trapped) to the and tend to H-bond with other elements, but hydrophobic residues can also cluster on the , either because this unfavorable structure is compensated by overall interactions or because those clusters form sites or interact with other non-polar groups.