Comparison between denaturant- and temperature-induced unfolding pathways of protein: A lattice Monte Carlo simulation

Denaturant-induced unfolding of protein is simulated by using a Monte Carlo simulation with a lattice model for protein and denaturant. Following the binding theory for denaturant-induced unfolding, the denaturant molecules are modeled to interact with protein by nearest-neighbor interactions. By analyzing the conformational states on the unfolding pathway of protein, the denaturant-induced unfolding pathway is compared with the temperature-induced unfolding pathway under the same condition; that is, the free energies of unfolding under two different pathways are equal. The two unfoldings show markedly different conformational distributions in unfolded states. From the calculation of the free energy of protein as a function of the number fraction (Q₀) of native contacts relative to the total number of contacts, it is found that the free energy of the largely unfolded state corresponding to low Q₀ (0.1 < Q₀ < 0.5) under temperature-induced unfolding is lower than that under denaturant-induced unfolding, whereas the free energy of the unfolded state close to the native state (Q₀ > 0.5) is lower in denaturant-induced unfolding than temperature-induced unfolding. A comparison of two unfolding pathways reveals that the denaturant-induced unfolding shows a wider conformational distribution than the temperature-induced unfolding, while the temperature-induced unfolding shows a more compact unfolded state than the denaturant-induced unfolding especially in the low Q₀ region (0.1 < Q₀ < 0.5).