Residue-dependent transition temperatures and denaturant midpoints in the folding of a multi-domain 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 multi-domain protein, Adenylate Kinase (ADK) with N = 214, in order to calculate thermal and denaturation unfolding titration curves. The results show that and are non-zero and follow the previously established ( Phys. Rev. Lett . 93 268107 (2004)) thermodynamic 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 .