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Residue-dependent transition temperatures and denaturant midpoints in the folding of a multi-domain protein

Liu, Z.; Thirumalai, D.

2022-10-08 biophysics
10.1101/2022.10.08.511446 bioRxiv
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As a consequence of the finite size of globular proteins, it is expected that there should be dispersions in the global melting temperature (Tm) and the denaturation midpoint (Cm). Thermodynamic considerations dictate that the dispersions, {Delta}Tm in Tm and {Delta}Cm in Cm, 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 [Formula] and [Formula] are non-zero and follow the previously established (Phys. Rev. Lett. 93 268107 (2004)) thermodynamic [Formula] scaling for proteins accurately. For ADK, the dispersions are small ({approx} 0.004), which implies that the melting temperature is more or less unique, which is unlike in BBL (N =40) where [Formula].

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