Why the protein may not reach final folded state Explain dis

Why the protein may not reach final folded state? Explain discussing energy landscape during folding.

Solution

According to the two-state protein model, the protein can exist either in folded or unfolded state, which follows the principle of all-or-none process. The cooperativity of protein folding determines the protein to be folded or unfolded. If the protein folding is very cooperative, any deviation from one interaction disrupts or destabilizes all other interactions.

The alpha helical proteins fold at a faster rate than the beta sheets. The helices follow the downhill folding, where the folding process do not require any energy inputs. Means, folding occurs by free energy in alpha helices, whereas, beta sheets more energy to separate the folded and unfolded states.

In case of alpha helices, the fixation of residues in their native conformation triggers the formation of hydrogen bonds. Means, the elongation process is thermodynamically favourable.

In contrast, in case of beta sheets, to stabilize one hydrogen bond, two peptide bonds are to be formed. Means, the folding process is (uphill) not thermodynamically favourable, side chain interactions stabilize the beta sheets, so a protein may not reach final folded state.