Adsorption characteristics of peptides on ω-functionalized self-assembled monolayers: a molecular dynamics study

Molecular dynamics simulations were employed to investigate the adsorption behavior of a variety of amino-acid side-chain analogs (SCAs) and a β-hairpin (HP7) peptide on a series of liquid-like self-assembled monolayers (SAMs) with terminal functional groups of -OH, -OCH₃, -CH₃, and -CF₃. The relationships between the adsorption free energy of the SCAs and the interfacial properties of water on the SAMs were examined to determine the acute predictors of protein adsorption on the SAM surfaces. The structural changes of HP7 on the SAM surfaces were also investigated to understand the relationship between the surface nature and protein denaturation. It was found that the adsorption free energy of the SCAs was linearly related to the surface hydrophobicity, which was computed as the free energy of cavity formation near the SAM-water interfaces. In addition, the hydrophobic -CH₃ and -CF₃ SAMs produced substantial conformational changes in HP7 because of the strong hydrophobic attractions to the nonpolar side chains. The hydrophilic surface terminated by -OH also promoted structural changes in HP7 resulting from the formation of hydrogen bonds between the hydrophilic tail and HP7. Consequently, the moderate amphiphilic surface terminated by -OCH₃ avoided the denaturation of HP7 most efficiently, thus improving the biocompatibility of the surface. In conclusion, these results provide a deep understanding of protein adsorption for a wide range of polymeric surfaces, and they can potentially aid the design of appropriate biocompatible coatings for medical applications.