Modeling‐Led Materials‐Binding Peptide Design for Hexagonal Boron Nitride Interfaces

Abstract Peptides that can bind specific nanomaterials with affinity and specificity are attractive for realizing a wide range of applications. Manipulation of biomolecule/2D‐material interfaces via noncovalent interactions in aqueous media has gained intensive attention due to the promising potential for biomolecule‐facilitated 2D‐material exfoliation, dispersion, and organization in water. Such advances have been recently achieved for graphene, where several peptide sequences have demonstrated this capability. However, few peptides are known specific binders of hexagonal boron nitride (h‐BN), resulting in a lack of fundamental knowledge regarding biomolecule/h‐BN interactions at the aqueous interface. To address this, enhanced sampling techniques are used to complete the set of interfacial adsorption free energies for all 20 amino acids, and a range of tripeptides. Based on these data, a reductionist approach is proposed to design new dodecapeptides anticipated to have stronger binding to h‐BN compared with a known h‐BN‐binding peptide, BP7, based on rearrangements of the tripeptide motifs within BP7. This hypothesis is tested using replica exchange with solute tempering molecular dynamics simulations, and the results indicate significantly increased surface contact for the two proposed BP7‐derived sequences. This work provides a rational, economical, and general approach to propose, design, and examine new material‐binding peptides based on their constituent properties.