Molecular dynamics simulations approach for the characterization of peptides with respect to hydrophobicity

It has been shown that molecular dynamics (MD) simulations are a powerful tool to generate knowledge about complex interactions in the field of bioprocess technologies at the atomic level. In this field, one of the most important nonspecific interactions is the hydrophobic interaction, which is still not fully understood after nearly 30 years of research. To date established hydrophobicity scales, which base mostly on proteins' primary structure, are used to estimate the overall hydrophobicity. The structural complexity and the influence of the protein's environment cannot be accommodated with these scales. In this work, free solution molecular dynamics simulations were used to investigate the hydrophobic character of low molecular weight peptides. Therefore, local densities of a small hydrophobic tracer molecule and unprotonated triethylamin (TEA) in particular were used to localize and quantify hydrophobic patches among the peptide surface. Comparisons between local densities and the retention behavior in reversed phase chromatography showed significant correlations. Moreover, neighbor effects caused by charges could be identified. We were able to show that the developed in silico method is applicable to characterize peptides in respect to hydrophobicity in agreement with experimental data. We are confident to apply this method to larger protein structures.