Probing the Molecular Mechanisms of Quartz-Binding Peptides

Abstract

Understanding the mechanisms of biomineralization and the realization of biology-inspired inorganic materials formation largely depends on our ability to manipulate peptide/solid interfacial interactions. Material interfaces and biointerfaces are critical sites for bioinorganic synthesis, surface diffusion, and molecular recognition. Recently adapted biocombinatorial techniques permit the isolation of peptides recognizing inorganic solids that are used as molecular building blocks, for example, as synthesizers, linkers, and assemblers. Despite their ubiquitous utility in nanotechnology, biotechnology, and medicine, the fundamental mechanisms of molecular recognition of engineered peptides binding to inorganic surfaces remain largely unknown. To explore propensity rules connecting sequence, structure, and function that play key roles in peptide/solid interactions, we combine two different approaches: a statistical analysis that searches for highly enriched motifs among de novo designed peptides, and, atomistic simulations of three experimentally validated peptides. The two strong and one weak quartz-binding peptides were chosen for the simulations at the quartz (100) surface under aqueous conditions. Solution-based peptide structures were analyzed by circular dichroism measurements. Small and hydrophobic residues, such as Pro, play a key role at the interface by making close contact with the solid and hindering formation of intrapeptide hydrogen bonds. The high binding affinity of a peptide may be driven by a combination of favorable enthalpic and entropic effects, that is, a strong binder may possess a large number of possible binding configurations, many of which having relatively high binding energies. The results signify the role of the local molecular environment among the critical residues that participate in solid binding. The work herein describes molecular conformations inherent in material-specific peptides and provides fundamental insight into the atomistic understanding of peptide/solid interfaces.

Silica Surface Features and Their Role in the Adsorption of Biomolecules: Computational Modeling and Experiments

“…Biocombinatorial techniques that were developped to select the «best» peptide sequences binding to a particular biochemical target have been applied to choose the best sequences for adsorption on inorganic surfaces. 271 In this way, quartz-binding peptides have been engineered 272 and sequences specific for amorphous silica have also been produced. 273 These studies are quickly generating a database of specific peptide sequences having more or less strong affinity with silica surfaces.…”

“…In order to evaluate the role of these residues in the interaction, classical MD simulations (CHARMM force field) of three peptides (two strong-binders and one weak-binder) in interaction with quartz (100) surface were carried out. 272,676 It was found that the strong-binding peptides exhibited the Pro-rich regions in close proximity to silica surface, and visual inspection revealed that these residues were buried at interstitial sites of quartz, whereas polar groups (Ser, His and C-terminus carboxylate)…”

Force Field and a Surface Model Database for Silica to Simulate Interfacial Properties in Atomic Resolution

“…19,[73][74][75][76] Sequence similarity is entirely random (5%) when the pH value varies in addition. Specific models for a given type of silica and conditions in solution are thus essential 19 and proposed here to cover the range of possible surface chemistry and ionization (Table 2).…”

Modeling and simulation of protein–surface interactions: achievements and challenges

“…A FF based on the CHARMM FF was parameterized by Lopes et al (2006) to obtain a structural and dynamic representation of water in the vicinity of neutral quartz crystalline surfaces using MD simulations. This FF was used for a set of peptides known to be strong and weak binders to the quartz (100) surface and showed that Pro, Trp and Leu were the main residues forming close contacts with the surface (Oren et al 2010).…”

“…REMD methods are useful to sample a large set of configurations in different potential wells separated by high energy barriers, which otherwise is not possible in a classical MD simulation. Indeed, temperature-based REMD (T-REMD) simulations were used in several studies to accelerate the sampling of peptide-surface interactions Li et al 2011;Oren et al 2010) and of interactions of basic fibroblast growth factor (bFGF), a small protein, with a hydroxyapatite (001) surface (Liao & Zhou, 2014). Liao and Zhou observed that while the protein displaces the surface hydration shell and binds tightly to the surface in the T-REMD simulations (five replicas in the range from 310 K to 2500 K), bFGF did not contact the surface directly in classical MD simulations at 310 K (Liao & Zhou, 2014).…”