Protein Folding in Vivo: From Anfinsen Back to Levinthal

Knowns and unknowns in the Davydov model for energy transfer in proteins

“…The feasibility of the ideas put forward in the previous paragraph was tested in the folding of a small protein. 36,73,74 Starting from an initial α-helix, it was shown that using the energy released in amide I decay to impulsively break the hydrogen bond linked to the previously excited CvO group, can lead to the bending of the helix and to the consequent folding of the initial helix into the helical hairpin that constitutes the native state of this protein. This shows that a localized delivery of energy can induce a large scale conformational change in a protein.…”

Statistical Evidence for a Helical Nascent Chain

“…Thus, instead of just a few amino acid patterns we can have many amino acid patterns that, in cells, lead to the same structural result (and the reverse can also happen, similar sequences can lead to different structures [22]). Another difficulty is that protein native structure may be one of the many kinetic traps into which the same polypeptide can find itself in, as shown in [23][24][25] and proposed in [26][27][28][29][30]. In this case, reproducibility in always reaching the same native structure can be achieved if the initial structure and the pathway followed from it are always the same, as explained in detail in [28].…”

“…Another difficulty is that protein native structure may be one of the many kinetic traps into which the same polypeptide can find itself in, as shown in [23][24][25] and proposed in [26][27][28][29][30]. In this case, reproducibility in always reaching the same native structure can be achieved if the initial structure and the pathway followed from it are always the same, as explained in detail in [28]. Thus, the purpose of our statistical analyses is to infer the structure of the nascent chain and of the generic features of the pathway.…”