The three states of globular proteins: acid denaturation.

摘要: We describe statistical mechanical theory that aims to predict protein stabilities as a function of temperature, pH, and salt concentration, from the physical properties constituent amino acids: (1) number nonpolar groups, (2) chain length, (3) temperature-dependent free energy transfer, (4) pKa's (including those in native state) their temperature dependencies. calculate here phase diagrams for apomyoglobin hypothetical variant proteins. The captures essential features stability including myoglobin's Tm vs pH measured by P. L. Privalov [(1979) Advances Protein Chemistry, Vol. 33, pp. 167-241] its ionic strength diagram Y. Goto A. Fink [(1990) Journal Molecular Biology, 214, 803-805]. main predictions are following: There three stable states, corresponding (N), compact denatured (C), highly unfolded (U), with transitions between them. In agreement experiments, state is predicted have enthalpy closer U than N because even though there considerable hydrophobic "clustering" C, this nevertheless represents major loss contacts relative configurations (N) "core." C becomes more prominent increasing content or decreasing perhaps thus accounting (a) why lysozyme alpha-lactalbumin differ (b) shortened Staph nuclease molecules compact. Of importance calorimetry Privalov's observation folding, delta H (T, pH) independent pH. accounts through prediction electrostatic contribution not enthalpic; entropy, mainly due different distributions protons small ions states.