LINKING RATES OF FOLDING IN LATTICE MODELS OF PROTEINS WITH UNDERLYING THERMODYNAMIC CHARACTERISTICS

We investigate the sequence-dependent properties of proteins that dete rmine the dual requirements of stability of the native stare and its k inetic accessibility using simple cubic lattice models. Three interact ion schemes are used to describe the potentials between nearest neighb or nonbonded beads. We show that, under the simulation conditions when the native basin of attraction (NBA) is the most stable, there is an excellent correlation between folding times tau(F) and the dimensionle ss parameter sigma(T) = (T-theta-T-F)/T-theta, where T-theta is the co llapse temperature and T-F is the folding transition temperature. Ther e is also a significant correlation between tau(F) and another dimensi onless quantity Z = (E-N-E-ms)/delta, where E-N is the energy of the n ative state, E-ms is the average energy of the ensemble of misfolded s tructures, and delta is the dispersion in the contact energies. In con trast, there is no significant correlation between tau(F) and the Z-sc ore gap Delta(Z) = E-N - E-ms. An approximate relationship between sig ma(T) and the Z-score is derived, which explains the superior correlat ion seen between tau(F) and sigma(T). For two state folders tau(F) is linked to the free energy difference (not simply energy gap, however i t is defined) between the unfolded states and the NEA. (C) 1998 Americ an institute of Physics. [S0021-9606(98)51134-8].