Single-point mutant perturbations have been dominantly used to probe protein folding mechanism experimentally, which turned -value into a critical parameter to infer the transition state ensemble. Recently, Munoz group’s large scale analysis of mutational effects showed a near single universal -value with normally distributed error for 24 proteins, and at zero stability conditions, the intrinsic variability0 is around 0.36. It provides some new understanding of protein folding based on -value probe. To detect which kind of interaction mechanism behind this, in the present study, we use native centric, explicit chain coarse-grained model, to systematically detect the perturbation of single-point mutations for four single domain two-state model proteins. The results indicate that the uniform, additive contact interactions could not conduce to the experimental Brønsted plot. Those significantly deviated from the main set points usually happen to terminal residues, and mostly are hydrophobic and formed contact with the other terminal fragment in native structure. By adjusting the native contact energetic heterogeneity and considering many-body interaction in the model, we found that these two elements might be important for more accurate understanding of protein folding.