The molecular interaction between protein and surfactant and its implication on the refolding of the protein in vitro was investigated by using the simple lattice model with dynamic Monte Carlo simulation and canonical ensemble.The thermodynamic feasible status of the model protein

as described by HP model

and its folding intermediates were captured. Some of the folding intermediates were trapped into local energy minimum and could not proceed refolding into the native form. The addition of surfactant enriched both the species and the amount of folding intermediates by the way of forming protein-surfactant complex. The surfactant of weak hydrophobicity had little impact on the thermodynamic status of the protein but was effective in moving the folding intermediates out of local minimum energy entrapment

leading to a considerable increase in the refolding. On the other hand

the surfactant with strong hydrophobicity might block the folding process by forming stable protein-surfactant complex. In this case

the dissociation of the complex by stripping the surfactant was necessary so as to precede the folding process. The synergy of surfactant and denaturing environment for protein refolding was also confirmed. The simulation agreed well with prior experiment results in literature. This indicated the potential of using molecular simulation to explore the details of refolding process and to assist the design of suitable surfactant-like folding aids.