Thermodynamic stability and kinetic foldability of a lattice protein model.

By using serial mutations, i.e., a residue replaced by 19 kinds of naturally occurring residues, the stability of native conformation and folding behavior of mutated sequences are studied. The 3 x 3 x 3 lattice protein model with two kinds of interaction potentials between the residues, namely the original Miyazawa and Jernigan (MJ) potentials and the modified MJ potentials (MMJ), is used. Effects of various sites in the mutated sequences on the stability and foldability are characterized through the Z-score and the folding time. It is found that the sites can be divided into three types, namely the hydrophobic-type (H-type), the hydrophilic-type (P-type) and the neutral-type (N-type). These three types of sites relate to the hydrophobic core, the hydrophilic surface and the parts between them. The stability of the native conformation for the serial mutated sequences increases (or decreases) as the increasing in the hydrophobicity of the mutated residues for the H-type sites (or the P-type sites), while varies randomly for the N-type sites. However, the foldability of the mutated sequences is not always consistent with the thermodynamic stability, and their relationship depends on the site types. Since the hydrophobic tendency of the MJ potentials is strong, the ratio between the number of the H-type sites and the number of the P-type sites is found to be 1:2. Differently, for the MJJ potentials it is found that such a ratio is about 1:1 which is relevant to that of real proteins. This suggests that the modification of the MJ potentials is rational in the aspect of thermodynamic stability. The folding of model proteins with the MMJ potentials is fast. However, the relationship between the foldability and the thermodynamic stability of the mutated sequences is complex.