Effects of surface hydrophobicity on the conformational changes of polypeptides of different length

We studied the effects of surface hydrophobicity on the conformational changes of different length polypeptides by calculating the free energy difference between peptide structures using the bias-potential Monte Carlo technique and the probability ratio method. It was found that the hydrophobic surface plays an important role in the stability of secondary structures of the polypeptides with hydrophobic side chains. For short GAAAAG peptides, the hydrophobic surface destabilizes the alpha helix but stabilizes the beta hairpin in the entire temperature region considered in our study. Interestingly, when the surface hydrophobic strength epsilon(hpsf) >= epsilon(hp), the most stable structure in the low temperature region changes from alpha helix to beta hairpin, and the corresponding phase transition temperature increases slightly. For longer GAAAAAAAAAAG peptides, the effects of the relatively weak hydrophobic surface (epsilon(hpsf) < epsilon(hp)) on alpha-helical structures may be neglected, while the relatively strongly hydrophobic surface (epsilon(hpsf) >= epsilon(hp)) leads to the obvious partial helicity loss. In contrast, the stability of beta structures can be enhanced significantly by the hydrophobic surface, especially by the strongly hydrophobic surface, at low and intermediate temperatures. At high temperatures, in addition to thermal fluctuations, the strongly hydrophobic surface (epsilon(hpsf) > epsilon(hp)) may further disturb the formation of both alpha-helical and beta structures. Moreover, the phase transition temperature between a-helical structures and random coils significantly decreases due to the helicity loss when epsilon(hpsf) > epsilon(hp). Our findings provide a basic and quantitative picture for understanding the effects of a hydrophobic surface on the conformational changes of the polypeptides with hydrophobic side chains. From an application viewpoint, the present study is helpful in developing alternative strategies of producing high-quality biological fibrillar materials and functional nanoscale devices by the self-assembly of the polypeptides on hydrophobic surfaces.