Molecular simulation study of 3,4-dihydroxyphenylalanine in the context of underwater adhesive design

Adhesives that can stick to multiple surface types in underwater and high moisture conditions are critical for various applications such as marine coatings, sealants, and medical devices. The analysis of natural underwater adhesives shows that L-3,4-dihydroxyphenylalanine (DOPA) and functional amyloid nanostructures are key components that contribute to the adhesive powers of these natural glues. The combination of DOPA and amyloid-forming peptides into DOPA-amyloid(-forming peptide) conjugates provides a new approach to design generic underwater adhesives. However, it remains unclear how the DOPA monomers may interact with amyloid-forming peptides and how these interactions may influence the adhesive ability of the conjugates. In this paper, we investigate the behavior of DOPA monomers, (glycine-DOPA)3 chains, and a KLVFFAE and DOPA-glycine chain conjugate in aqueous environments using molecular simulations. The DOPA monomers do not aggregate significantly at concentrations lower than 1.0M. Simulations of (glycine-DOPA)3 chains in water were done to examine the intra-molecular interactions of the chain, wherein we found that there were unlikely to be interactions detrimental to the adhesion process. After combining the alternating DOPA-glycine chain with the amyloid-forming peptide KLVFFAE into a single chain conjugate, we then simulated the conjugate in water and saw the possibility of both intra-chain folding and no chain folding in the conjugate.