Molecules of Life

How many different conformations can a protein adopt?

A lot. For a typical protein consisting of 100 amino acids, there are approximately 3198 possible conformational states. This leads to something called Levinthal’s paradox, which has to do with how a protein goes about sampling each of these possible states. If a protein just randomly went through each of 3198 possible states, it would, on average, take longer than the age of the universe to get through all of them!

Fortunately proteins don’t sample each of the possible conformations randomly. Instead, the gradient (or slope) of the energy along the folding pathway, along with the formation of local interactions between the amino acids, guides the protein toward states of lower energy. This allows it to avoid sampling most of the unimportant conformations as it folds toward its native state.


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