Factors that affect the folding ability of proteins

ABSTRACT The folding ability of a heteropoly-mer model for proteins subject to Monte Carlo dynamics on a simple cubic lattice is shown to be strongly correlated with the stability of the native state. We consider a number of estimates of the stability that can be determined without simula-tion, including the energy gap between the native state and the structurally dissimilar part of the spectrum (Z score) and, for sequences with fully compact native states, the gap in energy between the native and first excited fully compact states. These estimates are found to be more robust predic-tors of folding ability than a parameter s that requires simulation for its evaluation: s 5 1 2 Tf /Tu, where Tf is the temperature at which the fluctuation of an order parameter is at its maximum and Tu is the temperature at which the specific heat is at its maximum. We show that the interpretation of Tu as the collapse transition temperature is not correct in general and that the correlation between s and the folding ability arises from the fact that s is related to the energy gap (Z score). Protein