Residue-Dependent Transition Temperatures and Denaturant Midpoints in the Folding of a Multidomain Protein.

As a consequence of the finite size of globular proteins, it is expected that there should be dispersions in the global melting temperature ( T m ) and the denaturation midpoint ( C m ). Thermodynamic considerations dictate that the dispersions, Δ T m in T m , and Δ C m in C m , should decrease with N , the number of residues in the protein. We performed coarse-grained simulations of the self-organized polymer (SOP) model of the multidomain protein adenylate kinase (ADK) with N = 214 in order to calculate thermal and denaturation unfolding titration curves. The results show that Δ T m / T m and Δ C m / C m are nonzero and follow the previously established ( Phys. Rev. Lett. 2004, 93, 268107) thermodynamic 1/ N scaling for proteins accurately. For ADK, the dispersions are small (≈0.004), which implies that the melting temperature is more or less unique, which is unlike in BBL ( N = 40) where Δ T m / T m ≈ 0.03.