Molecular dynamics simulations of the interactions of potential foulant molecules and a reverse osmosis membrane

Reverse osmosis (RO) is increasingly one of the most common technologies for desalination worldwide. However, fouling of the membranes used in the RO process remains one of the main challenges. In order to better understand the molecular basis of fouling the interactions of a fully atomistic model of a polyamide membrane with three different foulant molecules, oxygen gas, glucose and phenol, are investigated using molecular dynamics simulations. In addition to unbiased simulations, umbrella sampling methods have been used to calculate the free energy profiles of the membrane-foulant interactions. The results show that each of the three foulants interacts with the membrane in a different manner.It is found that a build up of the two organic foulants, glucose and phenol, occurs at the membrane-saline solution, due to the favourable nature of the interaction in this region, and that the presence of these foulants reduces the rate of flow of water molecules over the membrane-solution interface. However, analysis of the hydrogen bonding shows that the origin of attraction of the foulant for the membrane differs. In the case of oxygen gas the simulations show that a build up of gas within the membrane is likely, although, no deterioration in the membrane performance was observed

Structural Disruption of an Adenosine-Binding DNA Aptamer on Graphene: Implications for Aptasensor Design

YesWe report on the predicted structural disruption of an adenosine-binding DNA aptamer adsorbed via noncovalent interactions on aqueous graphene. The use of surface-adsorbed biorecognition elements on device substrates is needed for integration in nanofluidic sensing platforms. Upon analyte binding, the conformational change in the adsorbed aptamer may perturb the surface properties, which is essential for the signal generation mechanism in the sensor. However, at present, these graphene-adsorbed aptamer structure(s) are unknown, and are challenging to experimentally elucidate. Here we use molecular dynamics simulations to investigate the structure and analyte-binding properties of this aptamer, in the presence and absence of adenosine, both free in solution and adsorbed at the aqueous graphene interface. We predict this aptamer to support a variety of stable binding modes, with direct base−graphene contact arising from regions located in the terminal bases, the centrally located binding pockets, and the distal loop region. Considerable retention of the in-solution aptamer structure in the adsorbed state indicates that strong intra-aptamer interactions compete with the graphene−aptamer interactions. However, in some adsorbed configurations the analyte adenosines detach from the binding pockets, facilitated by strong adenosine−graphene interactions

Elucidating the mechanisms of nanodiamond-promoted structural disruption of crystallised lipid

yesThe removal or structural disruption of crystallised lipid is a pivotal but energy-intensive step in a wide range of industrial and biological processes. Strategies to disrupt the structure of crystallised lipid in aqueous solution at lower temperatures are much needed, where nanoparticle-based strategies show enormous promise. Using the aqueous tristearin bilayer as a model for crystallised lipid, we demonstrate that the synergistic use of surfactant and detonation nanodiamonds can depress the onset temperature at which disruption of the crystallised lipid structure occurs. Our simulations reveal the molecular-scale mechanisms by which this disruption takes place, indicating that the nanodiamonds serve a dual purpose. First, the nanodiamonds are predicted to facilitate delivery of surfactant to the lipid/water interface, and second, nanodiamond adsorption acts to roughen the lipid/water interface, enhancing ingress of surfactant into the bilayer. We find the balance of the hydrophobic surface area of the nanodiamond and the nanodiamond surface charge density to be a key determinant of the effectiveness of using nanodiamonds to facilitate lipid disruption. For the nanodiamond size considered here, we identify a moderate surface charge density, that ensures the nanodiamonds are neither too hydrophobic nor too hydrophilic, to be optimal

Molecular dynamics simulations of mixed DOPC–β-sitosterol bilayers and their interactions with DMSO

ell membrane phospholipid bilayers can be damaged by the large amounts of dimethyl sulphoxide (DMSO) commonly used in cryopreservation. The interaction of DMSO with model bilayers consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and ß-sitosterol has been studied using molecular dynamics simulations. Initially the effect of sterol concentration and temperature upon bilayers solvated in pure water was determined, and membranes containing ß-sitosterol were compared with membranes containing cholesterol. These simulations showed that the presence of sterols has a condensing effect on the phospholipids, causing a reduction in the area per lipid as the sterol concentration increases, up to a phospholipid–sterol ratio of 2[thin space (1/6-em)]:[thin space (1/6-em)]1. The incorporation of sterols into the bilayer also increased the thickness and order of the phospholipid acyl tails. DOPC–ß-sitosterol bilayers at different relative concentrations were simulated in solutions of 2.5 and 25.0 mol% DMSO. The interaction of DMSO with the bilayers caused the bilayers to expand laterally, while thinning normal to the plane of the bilayer expansion. The same qualitative behaviour has been shown to occur in pure phosphocholine bilayers. However, the presence of sterols made the membranes more resistant to the effects of DMSO, to the extent that the membranes where able to maintain their integrity in 25.0 mol% DMSO, a concentration that would otherwise cause the destruction of a pure DOPC bilayer. Increasing the concentration of ß-sitosterol within the bilayers reduced the rate of DMSO diffusion across the bilayer and, if the concentration was large enough, caused the diffusion mechanism to change. DMSO was observed to disorder the membranes enough to cause an increase in the number of sterol “flip–flops”. The findings of this work provide a more realistic description of how DMSO interacts with cell membranes and the role of the composition of the membrane

Probing nano-patterned peptide self-organisation at the aqueous graphene interface

YesThe peptide sequence GrBP5, IMVTESSDYSSY, is found experimentally to bind to graphene, and ex situ atomic force microscopy indicates the formation of an ordered over-layer on graphite. However, under aqueous conditions neither the molecular conformations of the adsorbed peptide chains, nor the molecular-level spatial ordering of the over-layer, has been directly resolved. Here, we use advanced molecular dynamics simulations of GrBP5, and related mutant sequences, to elucidate the adsorbed structures of both the peptide and the adsorbed peptide over-layer at the aqueous graphene interface. In agreement with a previous hypothesis, we find GrBP5 binds at the aqueous graphene interface chiefly via the tyrosine-rich C-terminal region. Our simulations of the adsorbed peptide over-layers reveal that the peptide chains form an aggregate that does not evolve further into ordered patterns. Instead, we find that the inter-chain interactions are driven by hydrogen bonding and charge–charge interactions that are not sufficiently specific to support pattern formation. Overall, we suggest that the experimentally-observed over-layer pattern may be due to the drying of the sample, and may not be prevalent at the solvated interface. However, our simulations indicate sequence modifications of GrBP5 to promote over-layer ordering under aqueous conditions

Tristearin bilayers: structure of the aqueous interface and stability in the presence of surfactants

YesWe report results of atomistic molecular dynamics simulations of an industrially-relevant, exemplar triacylglycerol (TAG), namely tristearin (TS), under aqueous conditions, at different temperatures and in the presence of an anionic surfactant, sodium dodecylbenzene sulphonate (SDBS). We predict the TS bilayers to be stable and in a gel phase at temperatures of 350 K and below. At 370 K the lipid bilayer was able to melt, but does not feature a stable liquid–crystalline phase bilayer at this elevated temperature. We also predict the structural characteristics of TS bilayers in the presence of SDBS molecules under aqueous conditions, where surfactant molecules are found to spontaneously insert into the TS bilayers. We model TS bilayers containing different amounts of SDBS, with the presence of SDBS imparting only a moderate effect on the structure of the system. Our study represents the first step in applying atomistic molecular dynamics simulations to the investigation of TAG-aqueous interfaces. Our results suggest that the CHARMM36 force-field appears suitable for the simulation of such systems, although the phase behaviour of the system may be shifted to lower temperatures than is the case for the actual system. Our findings provide a foundation for further simulation studies of the TS-aqueous interface.vesk

What makes a good graphene-binding peptide? Adsorption of amino acids and peptides at aqueous graphene interfaces

YesInvestigation of the non-covalent interaction of biomolecules with aqueous graphene interfaces is a rapidly expanding area. However, reliable exploitation of these interfaces in many applications requires that the links between the sequence and binding of the adsorbed peptide structures be clearly established. Molecular dynamics (MD) simulations can play a key role in elucidating the conformational ensemble of peptides adsorbed at graphene interfaces, helping to elucidate these rules in partnership with experimental characterisation. We apply our recently-developed polarisable force-field for biomolecule–graphene interfaces, GRAPPA, in partnership with advanced simulation approaches, to probe the adsorption behaviour of peptides at aqueous graphene. First we determine the free energy of adsorption of all twenty naturally occurring amino acids (AAs) via metadynamics simulations, providing a benchmark for interpreting peptide–graphene adsorption studies. From these free energies, we find that strong-binding amino acids have flat and/or compact side chain groups, and we relate this behaviour to the interfacial solvent structuring. Second, we apply replica exchange with solute tempering simulations to efficiently and widely sample the conformational ensemble of two experimentally-characterised peptide sequences, P1 and its alanine mutant P1A3, in solution and adsorbed on graphene. For P1 we find a significant minority of the conformational ensemble possesses a helical structure, both in solution and when adsorbed, while P1A3 features mostly extended, random-coil conformations. In solution this helical P1 configuration is stabilised through favourable intra-peptide interactions, while the adsorbed structure is stabilised via interaction of four strongly-binding residues, identified from our metadynamics simulations, with the aqueous graphene interface. Our findings rationalise the performance of the P1 sequence as a known graphene binder.vesk

Non-covalent adsorption of amino acid analogues on noble-metal nanoparticles: influence of edges and vertices

YesThe operation of many nanostructured biomolecular sensors and catalysts critically hinges on the manipulation of non-covalent adsorption of biomolecules on unfunctionalised noble-metal nanoparticles (NMNPs). Molecular-level structural details of the aqueous biomolecule/NMNP interface are pivotal to the successful realisation of these technologies, but such experimental data are currently scarce and challenging to obtain. Molecular simulations can generate these details, but are limited by the assumption of non-preferential adsorption to NMNP features. Here, via first principles calculations using a vdW-DF functional, and based on nanoscale sized NMNPs, we demonstrate that adsorption preferences to NP features vary with adsorbate chemistry. These results show a clear distinction between hydrocarbons, that prefer adsorption to facets over edges/vertices, over heteroatomic molecules that favour adsorption onto vertices over facets. Our data indicate the inability of widely used force-fields to correctly capture the adsorption of biomolecules onto NMNP surfaces under aqueous conditions. Our findings introduce a rational basis for the development of new force-fields that will reliably capture these phenomena

Distinct differences in peptide adsorption on palladium and gold: introducing a polarizable model for Pd(111)

YesMaterials-binding peptides offer promising routes to the production of tailored Pd nanomaterials in aqueous media, enabling the optimization of catalytic properties. However, the atomic-scale details needed to make these advances are relatively scarce and challenging to obtain. Molecular simulations can provide key insights into the structure of peptides adsorbed at the aqueous Pd interface, provided that the force-field can appropriately capture the relevant bio-interface interactions. Here, we introduce and apply a new polarizable force field, PdP-CHARMM, for the simulation of biomolecule–Pd binding under aqueous conditions. PdP-CHARMM was parametrized with density functional theory (DFT) calculations, using a process compatible with similar polarizable force-fields created for Ag and Au surfaces, ultimately enabling a direct comparison of peptide binding modes across these metal substrates. As part of our process for developing PdP-CHARMM, we provide an extensive study of the performance of ten different dispersion-inclusive DFT functionals in recovering biomolecule–Pd(111) binding. We use the functional with best all-round performance to create PdP-CHARMM.We then employ PdP-CHARMM and metadynamics simulations to estimate the adsorption free energy for a range of amino acids at the aqueous Pd(111) interface. Our findings suggest that only His and Met favor direct contact with the Pd substrate, which we attribute to a remarkably robust interfacial solvation layering. Replica-exchange with solute tempering molecular dynamics simulations of two experimentally-identified Pd-binding peptides also indicate surface contact to be chiefly mediated by His and Met residues at aqueous Pd(111). Adsorption of these two peptides was also predicted for the Au(111) interface, revealing distinct differences in both the solvation structure and modes of peptide adsorption at the Au and Pd interfaces. We propose that this sharp contrast in peptide binding is largely due to the differences in interfacial solvent structuring.Air Force Office for Scientfi c Research (Grant #FA9550-12-1-0226

Effect of calcium ions on peptide adsorption at the aqueous rutile titania (110) interface

YesWe investigate how the presence of Ca2+ ions at the aqueous TiO2 interface influences the binding modes two experimentally-identified titania-binding peptides, Ti-1 and Ti-2, using replica exchange with solute tempering molecular dynamics simulations. We compare our findings with available experimental data and contrast our results with those obtained under NaCl solution conditions. We find that for Ti-1, Ca2+ ions enhances the adsorption of the negatively-charged Asp8 residue in this sequence to the negatively-charged surface, via Asp{Ca2+{TiO2 bridging. This appears to generate a non-local impact on the adsorption of Lys12 in Ti-1, which then pins the peptide to the surface via direct surface contact. For Ti-2, fewer residues were predicted to adsorb directly to the surface in CaCl2, compared with predictions made for NaCl solution, possibly due to competition between the other peptide residues and Ca2+ ions to adsorb to the surface. This reduction in direct surface contact gives rise to a more extensive solvent-mediated contact Ti-2. In general, the presence of Ca2+ ions resulted in a loss of conformational diversity of the surface-adsorbed conformational ensembles of these peptides, compared to counterpart data predicted for NaCl solution. Our findings provide initial insights into how peptide{TiO2 interactions might be tuned at the molecular level via modification of the salt composition of the liquid medium.Air Office of Scientific Research, grant number FA9550-12-1- 0226