Introduction to Biochemistry - Quiz 2.2.3

The Levinthal's paradox is about the combinatorial complexity of conformation. If there are 100 bonds that can be rotated, and even if we simplify the possible rotation to just 3 choices, there will be $ 3^{100} $ rotations, that's a huge number. But protein can fold into an unique native fold. If the folding process goes through all possible conformation, that will takes forever.

Therefore protein folding must be a guided process, it cannot possibly be sampling all possible conformations.

The answer is "A protein would essentially never find its native fold by sampling all possible conformations".

It is fun to repeat the math here. Assuming 100 bonds, 3 configuration per bond, and 0.1 ps for sampling a configuration.

The time required is $ \frac{(3^{100}) \times 0.1 \times 10^{-12}}{60 \times 60 \times 365} $ years. One can easily compute the value using logarithm and it is $ 10^{28} $ years, similar but not exactly equal to the value given in the lecture.

=100 * log(3) + log(0.1) - 12 * log(10) - log(60) - log(60) - log(365.25)

As discussed above, the protein folding process is guided. By what? By far, the dominating folding driver is the hydrophobic effect. Once the hydrophobic effect kicks in and bring the hydrophobic groups together, now the molecule is getting close and other interaction can happen. This is cooperation.

The answer is "There is a high degree of cooperativity in protein folding".

The first answer is wrong because we know free energy difference does to explain the speed of the process. Burning tree can release a lot of energy, but until someone set a fire a tree will practically never burns.

The third answer is not true either, we know pure protein sample folds itself  in aqueous solution.

The fourth answer is close, but not quite, many of the amino acid do not have a charged side chain, the only charge that always exists is at the terminals, that is just too far away - even if the salt bridge interaction "force" is large, the "chance" for them to be in reasonable proximity is low.

This is my original words when I replied on the website and it is accepted.

Diffusion collision forms secondary structures first, and then rearrange to get to the final fold. Nucleation condensation forms the hydrophobic core first, and then form the secondary structures.