The following is a long article in wikibooks, but it does explain the constraining biological processes that constrain protein folding as process that as the article concludes;
"We now know that while protein folding is not a random process . . . "
Please note
"not a random process."
Structural Biochemistry/Proteins/Protein Folding - Wikibooks, open books for an open world
Determinants of Protein Folding
There are various interactions that help stabilize structures of native proteins. Specifically, it is important to examine how the interactions that form protein structures are organized. In addition, there are only a small amount of possible polypeptide sequences that allow for a stable conformation. Therefore, it is evident that specific sequences are used through evolution in biological systems.
Helices and Sheets Predominate in Proteins because They Efficiently Fill Space
On average, about sixty percent of proteins contain a high amount of
alpha helices, and
beta pleated sheets. Through hydrophobic interactions, the protein is able to achieve compact nonpolar cores, but they lack the ability to specify which polypeptides to restrict in particular conformations. As seen in polypeptide segments in the coil form, the amount of hydrogen boding is not lesser than that of alpha helices and beta pleated sheets. This observation demonstrates that the different kinds of conformations of polypeptides are not limited by hydrogen bonding requirements.
Ken Dill has suggested that helices and sheets occur as a result of the
steric hindrance in condensed polymers. Through experimentation and simulation of conformations with simple flexible chains, it can be determined that the proportion of beta pleated sheets and alpha helices increase as the level of complication of chains is increased. Therefore, it can be concluded that helices and sheets are important in the complex structure of a protein, as they are compact in protein folding. The coupling of different forces such as
hydrogen bonding, ion pairing, and
van der Waals interactions further aids in the formation of alpha helices and beta sheets.
Protein Folding is Directed by Internal Residues
By investigating protein modification, the role of different classes of amino acid residues in protein folding can be determined. For example, in a particular study the free primary amino groups of RNase A were
derivatized with poly-DL-alanine which consist of 8 residue chains. The poly-Ala chains are large in size and are water-soluble, thus allowing the RNase's 11 free amino groups to be joined without interference of the native structure of the protein or its ability to refold. As a result, it can be concluded that the protein's internal residues facilitates its native conformation because the RNase A free amino groups are localized on the exterior. Furthermore, studies have shown that mutations that occur on the surface of residues are common, and less likely to change the protein conformation compared to changes of internal residues that occur. This finding suggests that protein folding is mainly due to the
hydrophobic forces.
Protein Structures Are Hierarchically Organized
George Rose demonstrated that protein domains consisted of subdomains, and furthermore have sub-subdomains, and etc. As a result, it is evident that large proteins have domains that are continuous, compact, and physically separable. When a polypeptide segment within a native protein is visualized as a string with many tangles, a plane can be seen when the string is cut into two segments. This process can be repeated when n/2 residues of an n-residue domain is highlighted with a blue and red color. As this process is repeated it can be seen that at all stages, the red and blue areas of the protein do not interpenetrate with one another. The following
link shows an X-ray structure of HiPIP (high potential iron protein) and its first n/2 residues on the n-residue protein colored red and blue. Furthermore, the subsequent structures shown in the second and third row show this process of n/2 residue splitting reiterated as shown where the left side of the protein has its first and last halves with red and blue while the rest of the chain colored in gray. Through this example, it is clearly seen that protein structures are organized in a hierarchical way, meaning that the polypeptide chains are seen as sub-domains that are themselves compact structures and interact with adjacent structures. These interactions forms a larger well organized structure largely due to
hydrogen bonding interactions and has an important role in understanding how
polypeptides fold to form their native structure.
