An explicit droplet calculation is developed to address two aspects of the folding kinetics of large proteins: the thermodynamic folding barrier and the reconfiguration rate. First, a nonspecific folding nucleus is described as the instanton or droplet solution of a free energy functional derived for a minimally frustrated polymer Hamiltonian of the Gō type. Second, a theory for the barriers for transitions between trapped misfolded states is developed using a replica approach extended to inhomogeneous cases near the glass transition temperature of a random heteropolymer. Replica instantons are computed and their shape described. These two factors are then combined to give a microscopic theory of the folding time.

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