In Vivo, A Typical Multi-domain Protein Will Conform Each Domain As It

In vivo, a typical multi-domain protein will conform each domain as it emerges, often within seconds of emergence. Alpha-helices and beta-sheets will typically form quickly in rough alignment and produce a structure called a molten globule (Alberts et al. 2002). It is from this structure that the final adjustments will take place until the correct tertiary structure is arrived at perhaps several minutes later.

It has to be remembered that the protein is basically a long chain which, in itself may take many minutes to fully emerge from the ribosome, so much of the initial folding will be complete by the time that the C-terminal emerges from the ribosome.

The situation is taken a little further by Demchenko (2000). He has suggested that it was formerly believed that protein molecules would normally assume their tertiary structure and then, normally, remain stable until denatured and destroyed. He takes the view that the protein should be considered a highly flexible molecular structure and that the formation of various protein-protein complexes is a dynamic process that occurs through a series of programmed steps of mutually varying conformation. It was known that when two proteins interacted they could, and did, change their overall quaternary structure but Demchenko suggests that this change of conformation can occur with the proteins at a substantial distance apart.

In a very new paper Berloff (April 2005) describes a mechanism which converts the protein's primary conformation into its secondary conformation. She argues that the mechanics of folding are ultimately determined by the local potential energy of the various amino acids in the polypeptide chain. She makes an analogy of spring tension in the chain which is due to the internal hydrogen bonds that are responsible for the formation of the alpha-helices and beta-sheets. She has computed conformational energy fields for various proteins that determine the eventual shape of that protein.
Chaperones
Chaperones are proteins that exist to help molecular folding of the newly formed protein molecule. In the majority of cases, if left alone for long enough, and in great enough dilution so that the molecules didn't interact, the new protein would adopt its final shape without help. The hydrophobic side-chains however, would cause considerable disruption within the aqueous melieu of the cytoplasm because (as we have related earlier) they will tend to congregate together to avoid direct exposure to the intracellular water. This is a physical process rather than a chemical one, and will occur when hydrophobic side-chains come into close proximity. If this should occur when two unrelated proteins should happen to be produced in the same vicinity, then they would tend to clump together and neither one would then be able to either fold or function correctly.