Protein folding mechanisms secondary structure formation

There are immense challenges also to model protein function, which will rely on better theoretical models for secondary structure formation (a helices, p sheets). Models presently used are molecular force field approaches, which are rather phenomenological. Realistic atomistic modelling is a long-term goal. In the meantime, energy landscape approaches should help us elucidate the detailed folding mechanisms that lead to protein function. 

C. dementi, A. E. Garcia, J. N. Onuchic (2003) Interplay among tertiary contacts, secondary structure formation and side-chain packing in the protein folding mechanism All-atom representation study of protein L. J. Mol. Biol. 326, pp. 933-954... 

Tertiary Contacts, Secondary Structure Formation and Side-chain Packing in the Protein Folding Mechanism All-atom Representation Study of Protein L. 

An interesting application of SDEL involved the folding mechanism of cytochrome The folding kinetics of cytochrome c has been studied extensively by a variety of experimental techniques. " The SDEL folding trajectories agree with several experimental observations including (1) the collapse of the protein without formation of secondary structures followed by formation of the terminal helices before the middle helix (see upper side of Figure 12),... 

A key feature of the framework and nucleation-condensation models is the formation of secondary structure—which might or might not be coupled to the formation of tertiary structure—early in the folding process. It follows that a full description of the mechanism of protein folding also requires an understanding of the rules that stabilize molecular interactions in polypeptides. We consider these rules in Chapter 11. 

The polypeptide chains of all proteins are synthesized by the process described above. This mechanism gives rise to primary polypeptide chains, which are often further modified—for example, by cleavage into smaller peptides, by stmctural modification of selected amino acid residues, by splicing of the polypeptide chain, or by the formation of covalent bonds between polypeptide chains. Some of these secondary modifications are related to the correct folding of polypeptide chains and to the production of active enzymes or peptide hormones from inactive precursors (e.g., insulin from proinsulin). Also, the transport of proteins within the cell or the secretion of extracellular proteins is often linked to structural changes in polypeptide chains either during or after completion of synthesis. 

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