Nucleation theory for helix unfolding in peptide chains.

This work introduces a microscopic nucleation theory of helix unfolding in peptide chains aimed at obtaining a semiempirical estimation of the critical-size bubble of structural distortion which may function as the kernel for helix destruction. A dynamic nucleation model for helix-coil transition has been previously introduced as an ansatz to estimate the kinetic barrier of the helix-unfolding event [A. Fernández and A. Colubri, J. Math. Phys. 39, 3167 (1998)]. However, the critical size of the helix-destruction bubble, empirically obtained from computer simulations of favored folding pathways, has not been hitherto justified or determined from first principles. This requires introducing a microscopic treatment of the long-time torsional dynamics to assess its bearing on the formation of structural-distortion bubbles which eventually trigger the helix-unfolding process. To reach this goal we introduce two operational tenets: (a) The torsional dynamics of the chain may be coarse grained according to a discretization of the conformational state of each unit, resolved according to its significant torsional isomers; (b) the semiempirical formulation accounts for the known dependence of the enthalpy increment due to helix unfolding on the change in the effective solvent-exposed surface area. The functional dependence on bubble size of the mean time of completion of the rate-determining step for helix unwinding is shown to be in agreement with previous ad hoc macroscopic models. However, in contrast with such treatments, we infer the existence of a denaturation temperature from the dynamics of critical bubble formation, rather than introducing it as an a priori postulate. Our determination of the critical temperature based on nucleation kinetics theory of critical bubble formation coincides with those obtained from calorimetric and spectroscopic measurements.