Biomolecular Recognition Principles for Bionanocombinatorics: An Integrated Approach To Elucidate Enthalpic and Entropic Factors

Abstract

Bionanocombinatorics is an emerging field that aims to use combinations of positionally encoded biomolecules and nanostructures to create materials and devices with unique properties or functions. The full potential of this new paradigm could be accessed by exploiting specific noncovalent interactions between diverse palettes of biomolecules and inorganic nanostructures. Advancement of this paradigm requires peptide sequences with desired binding characteristics that can be rationally designed, based upon fundamental, molecular-level understanding of biomolecule-inorganic nanoparticle interactions. Here, we introduce an integrated method for building this understanding using experimental measurements and advanced molecular simulation of the binding of peptide sequences to gold surfaces. From this integrated approach, the importance of entropically driven binding is quantitatively demonstrated, and the first design rules for creating both enthalpically and entropically driven nanomaterial-binding peptide sequences are developed. The approach presented here for gold is now being expanded in our laboratories to a range of inorganic nanomaterials and represents a key step toward establishing a bionanocombinatorics assembly paradigm based on noncovalent peptide-materials recognition.

Aqueous Peptide–TiO2 Interfaces: Isoenergetic Binding via Either Entropically or Enthalpically Driven Mechanisms

“…The adsorption curve of each peptide at varying concentrations was fitted using a Langmuir isotherm, allowing values for kobs to be determined. 5 By utilising QCM-D data, the layer thickness of the peptide overlayer can be approximated 60 provided the effective density of the adhering layer is known. This density value was estimated by implementing the method reported by Fischer et al 61 Full details of these calculations are provided in "Overlayer Thickness Estimates from QCM-D data" in the Supporting Information.…”

“…As described by Tang et. al, 5 the binding affinity of a particular sequence is characterized by the difference in Gibbs free energy between the bound and unbound states, ΔG =ΔH -TΔS, which is related to the equilibrium constant for binding, Keq = exp[ΔG/(RT)], where T denotes temperature. In previous studies, the high affinity of both peptides for TiO2 surfaces was suggested to be responsible for the formation of nanometer-sized crystalline nanoparticles of titania via a capping mechanism.…”

“…5 Additionally, our previous work suggests that strong binding affinity can also arise from the system possessing many different adsorbed conformations, of which the degree of disorder in the adsorbed state is an indicative metric. 5 Our clustering analysis provides an estimate of this degree of disorder in the surface-adsorbed state. In this sense, the favourable binding energy of Ti-1 is in part facilitated by the large number of thermally-available, structurally-distinct adsorbed peptide conformations.…”

“…[1][2][3][4] Use of bioinspired approaches to realize the nucleation, growth and functionalization of materials in aqueous media, principally by the addition of peptides [5][6] shows exciting promise, and has become the subject of intense scrutiny for a range of materials 7 , such as noble metals, [8][9] graphene [10][11] and silica, 12 in addition to titania (TiO2).…”

“…However, a significant obstacle to developing versatile and reliable peptide-based strategies for the generation and organization/activation of nanostructured inorganic materials is our limited understanding of how to exploit the relationship between peptide sequence and corresponding materials-binding affinity. 5,17 To this end, a deeper understanding of the physical provenance of peptide-materials recognition is much needed to advance protocols for the peptide-based generation and organization of nanostructured inorganic materials.…”