The Influence of Amino Acid Sequence and Functionality on the Binding Process of Peptides onto Gold Surfaces

Abstract

We present a molecular dynamics study of the binding process of peptide A3 (AYSSGAPPMPPF) and other similar peptides onto gold surfaces, and identify the functions of many amino acids. Our results provide a clear picture of the separate regimes present in the binding process: diffusion, anchoring, crawling and binding. Moreover, we explored the roles of individual residues. We found that tyrosine, methionine, and phenylalanine are strong binding residues; serine serves as an effective anchoring residue; proline acts as a dynamic anchoring point, while glycine and alanine give flexibility to the peptide backbone. We then show that our findings apply to unrelated phage-derived sequences that have been reported recently to facilitate AuNP synthesis. This new knowledge may aid in the design of new peptides for the synthesis of gold nanostructures with novel morphologies.

Functional and Selective Bacterial Interfaces Using Cross-Scaffold Gold Binding Peptides

“…These similarities in flexibility and lack of innate structure are consistent with our experimental results, which do not discriminate binding on gold between these three systems. The Midas-2 structures are also similar to previously published data of this peptide binding on gold, 57 which highlight the flexible middle Val-Leu-Ile-Ala segment (clearly visible in Fig. 3c) and the possible role it plays in the binding process.…”

“…26,57,58,67,78 It is clear from Fig. 3 that all three peptides are lacking in helical propensity and avoid any overwhelming structural characteristics which could interfere in the binding process.…”

“…However, the segments on either side of this bend are completely flexible and this small structure is not expected to impede the binding process in any meaningful way. It is possible that these proline residues contribute to the 'dynamic anchoring' seen by Yu et al 57 An analysis of the backbone RMSD during the course of a 30 ns trajectory allows comparison of the overall RMSD for each peptide, showing that while Midas-2 is somewhat more flexible, all three peptides show a similar degree of flexibility. These similarities in flexibility and lack of innate structure are consistent with our experimental results, which do not discriminate binding on gold between these three systems.…”

“…Although much of this work has been designed to isolate properties contributing to successful binding (e.g., flexibility, electrostatics, solvent interactions), it has remained difficult to distill this into a concise set of design principles. 36,53,54 In order to probe the origins of the predominance of hydroxyl-containing amino acids with gold surfaces, Calzolari et al 55 performed ab initio molecular dynamics (AIMD) of a hydroxyl containing b-sheet-forming peptide, and found that cooperativity between serine side chains and solvent molecules contributed to successful 57 suggested that Tyr, Met, and Phe are strong binders, while serine breaks through the hydration layer to form an anchor point. Verde et al 58 performed further molecular dynamics to study the role of flexibility and stability in adsorption of known gold-binding and non-gold-binding peptides.…”

“…It is possible that the slightly improved affinity of peptide p8#9 for gold may be attributed to the larger number of serines in this peptide. It has been previously noted 55,57 that the interactions of hydroxyl-containing residues play an important role in providing access to the surface, thus allowing opportunity for binding. Less is known about silicon-specific binding residues in the literature.…”