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, ΔT_m in T_m, and ΔC_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 ΔT_m/T_m and ΔC_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 ΔT_m/T_m ≈ 0.03.