Amino acid interactions dependent on the polymerization of charged residues and surface properties of monolayers

Abstract

Charged amino acids are the key residues that regulate protein function and stability, and successive sequences of charged amino acids contribute significantly to protein assembly. Therefore, an in-depth understanding of the strengths and manners of amino acid-amino acid interactions (AAIs) caused by successive sequences of charged residues is required. In this study, we prepared self-assembled monolayers (SAMs) bearing charged alkanethiols as ligands to mimic protein surfaces with accumulated charged amino acids. Moreover, we used amino acid peptides as analytes to evaluate the AAIs based on chain length. The strengths of the AAIs of tri- and tetrapeptides varied per residue, depending on the properties of the SAMs, such as their densities and hydrophobicities, whereas those of mono- and dipeptides did not vary significantly. Remarkably, the strengths of the AAIs per residue decreased significantly with increasing peptide length, even when the strengths of the AAIs increased at the peptide scale. These results enabled us to quantify the microscopic changes in the AAIs, in addition to the overall interactions governed by the reaction field and alignment of the charged amino acids. Our analysis of AAIs shall be beneficial in protein engineering via genetic mutations based on charged amino acids.