Roles of native topology and chain-length scaling in protein folding: a simulation study with a Go-like model.

We perform folding simulations on 18 small proteins with using a simple Go-like protein model and analyze the folding rate constants, characteristics of the transition state ensemble, and those of the denatured states in terms of native topology and chain length. Near the folding transition temperature, the folding rate k(F) scales as k(F) approximately exp(-c RCO N(0.6)) where RCO and N are the relative contact order and number of residues, respectively. Here the topology RCO dependence of the rates is close to that found experimentally (k(F) approximately exp(-c RCO)), while the chain length N dependence is in harmony with the predicted scaling property (k(F) approximately exp(-c N(2/3))). Thus, this may provides a unified scaling law in folding rates at the transition temperature, k(F) approximately exp(-c RCO N(2/3)). The degree of residual structure in the denatured state is highly correlated with RCO, namely, proteins with smaller RCO tend to have more ordered structure in the denatured state. This is consistent with the observation that many helical proteins such as myoglobin and protein A, have partial helices, in the denatured states. The characteristics of the transition state ensemble calculated by the current model, which uses native topology but not sequence specific information, are consistent with experimental phi-value data for about half of proteins. Copyright 2001 Academic Press.