What statement most accurately describes the thermodynamic hypothesis? Proteins have numerous equally thermodynamically stable conformations, including the most unfolded and folded forms. The thermodynamically stable conformation of a protein is its native fold. Advanced understanding of protein thermodynamics allows us to accurately predict the folded structure of any protein. The native fold of a protein is determined by a combination of thermodynamic and kinetic parameters.
The Correct Answer and Explanation is:
Correct answer:
The thermodynamically stable conformation of a protein is its native fold.
Explanation:
The thermodynamic hypothesis, also known as Anfinsen’s hypothesis, proposes that the three-dimensional structure of a protein, known as its native fold, is determined by the protein’s amino acid sequence and that this structure represents the lowest free energy state under physiological conditions. In other words, the native conformation is the most thermodynamically stable form of the protein.
This idea was famously supported by experiments on ribonuclease A conducted by Christian Anfinsen. When the protein was denatured using agents like urea and then these agents were removed, the protein refolded spontaneously back into its active form. This indicated that all the information required for correct folding was contained within the primary sequence of the protein and that the folding pathway was driven by thermodynamics.
The hypothesis implies that a protein does not randomly sample all possible conformations, which would take an impractically long time, but rather follows a directed folding pathway toward the lowest energy state. Misfolded or intermediate states are generally higher in free energy and less stable than the native form.
This hypothesis does not support the idea that proteins have many equally stable conformations. Nor does it claim that accurate prediction of protein structure is currently possible for all proteins, although modern computational tools are advancing rapidly. Also, the hypothesis emphasizes thermodynamics rather than kinetic factors. While kinetics can influence how quickly or slowly folding occurs and may sometimes lead to metastable states, the final stable structure is primarily determined by thermodynamic stability.
Therefore, the most accurate description of the thermodynamic hypothesis is that the native fold of a protein corresponds to its thermodynamically most stable conformation.
