Zak E. Hughes

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

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.

Biomolecular Adsorption at Aqueous Silver Interfaces: First-Principles Calculations, Polarizable Force-Field Simulations, and Comparisons with Gold

The molecular simulation of biomolecules adsorbed at noble metal interfaces can assist in the development of bionanotechnology applications. In line with advances in polarizable force fields for adsorption at aqueous gold interfaces, there is scope for developing a similar force field for silver. One way to accomplish this is via the generation of in vacuo adsorption energies calculated using first-principles approaches for a wide range of different but biologically relevant small molecules, including water. Here, we present such first-principles data for a comprehensive range of bio-organic molecules obtained from plane-wave density functional theory calculations using the vdW-DF functional. As reported previously for the gold force field, GolP-CHARMM (Wright, L. B.; Rodger, P. M.; Corni, S.; Walsh, T. R. GolP-CHARMM: first-principles based force-fields for the interaction of proteins with Au(111) and Au(100). J. Chem. Theory Comput. 2013, 9, 1616-1630), we have used these data to construct a a new force field, AgP-CHARMM, suitable for the simulation of biomolecules at the aqueous Ag(111) and Ag(100) interfaces. This force field is derived to be consistent with GolP-CHARMM such that adsorption on Ag and Au can be compared on an equal footing. Our force fields are used to evaluate the water overlayer stability on both silver and gold, finding good agreement with known behaviors. We also calculate and compare the structuring (spatial and orientational) of liquid water adsorbed at both silver and gold. Finally, we report the adsorption free energy of a range of amino acids at both the Au(111) and Ag(111) aqueous interfaces, calculated using metadynamics. Stronger adsorption on gold was noted in most cases, with the exception being the carboxylate group present in aspartic acid. Our findings also indicate differences in the binding free energy profile between silver and gold for some amino acids, notably for His and Arg. Our analysis suggests that the relatively stronger structuring of the first water layer on silver, relative to gold, could give rise to these differences.

Sequence-Dependent Structure/Function Relationships of Catalytic Peptide-Enabled Gold Nanoparticles Generated under Ambient Synthetic Conditions

Peptide-enabled nanoparticle (NP) synthesis routes can create and/or assemble functional nanomaterials under environmentally friendly conditions, with properties dictated by complex interactions at the biotic/abiotic interface. Manipulation of this interface through sequence modification can provide the capability for material properties to be tailored to create enhanced materials for energy, catalysis, and sensing applications. Fully realizing the potential of these materials requires a comprehensive understanding of sequence-dependent structure/function relationships that is presently lacking. In this work, the atomic-scale structures of a series of peptide-capped Au NPs are determined using a combination of atomic pair distribution function analysis of high-energy X-ray diffraction data and advanced molecular dynamics (MD) simulations. The Au NPs produced with different peptide sequences exhibit varying degrees of catalytic activity for the exemplar reaction 4-nitrophenol reduction. The experimentally derived atomic-scale NP configurations reveal sequence-dependent differences in structural order at the NP surface. Replica exchange with solute-tempering MD simulations are then used to predict the morphology of the peptide overlayer on these Au NPs and identify factors determining the structure/catalytic properties relationship. We show that the amount of exposed Au surface, the underlying surface structural disorder, and the interaction strength of the peptide with the Au surface all influence catalytic performance. A simplified computational prediction of catalytic performance is developed that can potentially serve as a screening tool for future studies. Our approach provides a platform for broadening the analysis of catalytic peptide-enabled metallic NP systems, potentially allowing for the development of rational design rules for property enhancement.

A computational investigation of the properties of a reverse osmosis membrane

Reverse osmosis (RO) is currently one of the most widely used methods of desalination in the world and rapidly increasing in usage. The membranes used in the RO process play a vital role in determining the effectiveness of the desalination process. In this work, fully atomistic molecular dynamics simulations of one of the most widely employed membranes, namely the FT30 polyamide material, have been carried out in order gain greater understanding of the structure of the system and its interaction with saline solution. The system studied consisted of a solvated membrane layer and a layer of bulk solution, thus allowing the membrane interface to be simulated. The behaviour of water and salt ions in both the bulk solution and membrane has been investigated. It was found that the diffusivities of water and the salt ions were reduced by an order of magnitude within the membrane. Furthermore, umbrella sampling methods have been used in order to determine the free energy surface associated with the salt ions passing through the membrane-solution interface. The present work demonstrates that there is a high degree of variability in the resistance to salt diffusion into the membrane associated with the structure of the water encountered as the ion permeates the membrane. Despite this variability in the free energy gradient, all cases ultimately exhibit a high resistance to ionic diffusion due to charge separation. However, migration of a sodium cation/chloride anion pair fails to substantially lower the barrier to salt diffusion, thus confirming the robust nature of the membrane selectivity for water.

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

Investigation 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.

Molecular dynamics simulations of the interactions of DMSO with DPPC and DOPC phospholipid membranes

Molecular dynamics simulations have been used to investigate the effect of DMSO on 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) phospholipid bilayers. The concentration of DMSO was varied between 0 and 25.0 mol %. For both lipids, DMSO causes the membrane to expand in the plane of the membrane while thinning normal to that plane. Above a critical concentration, pores in the membrane form spontaneously, and if the concentration is increased further, then the bilayer structure is destroyed. Even at concentrations below those required to induce pores, DMSO readily diffuses across the bilayers. The free-energy profile associated with the diffusion of a DMSO molecules across the membrane has been calculated. The simulations suggest that the DOPC bilayer is more resistant to the deleterious effects of DMSO, both increasing the stability of the membranes and decreasing the rate at which DMSO diffuses across the membrane. In this way, the work highlights the importance of investigating the lipid composition of cell membranes when characterizing the effects of cryosolvents.

Efficient simulations of the aqueous bio-interface of graphitic nanostructures with a polarisable model

To fully harness the enormous potential offered by interfaces between graphitic nanostructures and biomolecules, detailed connections between adsorbed conformations and adsorption behaviour are needed. To elucidate these links, a key approach, in partnership with experimental techniques, is molecular simulation. For this, a force-field (FF) that can appropriately capture the relevant physics and chemistry of these complex bio-interfaces, while allowing extensive conformational sampling, and also supporting inter-operability with known biological FFs, is a pivotal requirement. Here, we present and apply such a force-field, GRAPPA, designed to work with the CHARMM FF. GRAPPA is an efficiently implemented polarisable force-field, informed by extensive plane-wave DFT calculations using the revPBE-vdW-DF functional. GRAPPA adequately recovers the spatial and orientational structuring of the aqueous interface of graphene and carbon nanotubes, compared with more sophisticated approaches. We apply GRAPPA to determine the free energy of adsorption for a range of amino acids, identifying Trp, Tyr and Arg to have the strongest binding affinity and Asp to be a weak binder. The GRAPPA FF can be readily incorporated into mainstream simulation packages, and will enable large-scale polarisable biointerfacial simulations at graphitic interfaces, that will aid the development of biomolecule-mediated, solution-based graphene processing and self-assembly strategies.

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.

An investigation of soft-core potentials for the simulation of mesogenic molecules and molecules composed of rigid and flexible segments

Abstract The phase behaviour of three soft core spherocylinder models is investigated with a view to producing an effective potential for use in coarse-grained simulations of liquid crystal phases and polymers composed of rigid and flexible segments. Provided potentials are not made too soft, two of the soft core models are found to work well in terms of successfully reproducing mesophases and in providing considerable improvements in computational speed over other commonly used coarse-grained models. In Monte Carlo simulations a soft-core spherocylinder model in which a cut and shifted Lennard–Jones potential is truncated with a linear tangential potential is found to be particularly effective; while for molecular dynamics a better model is provided by a DPD-like quadratic potential. Here, computational speed-ups of 20 – 30 × are seen in equilibration times in comparison to the well-known soft repulsive spherocylinder (SRS) model. The quadratic potential is used in an additional set of coarse-grained simulations of a liquid crystal with a flexible chain, which exhibits spontaneous formation of a nematic phase. The use of different types of interaction sites is also illustrated by the simulation of a spherocylinder with two “tails” formed from spheres. Here, varying the hardness of the sphere-spherocylinder interaction potential allows the formation of a smectic-A phase which exhibits microphase separation.

Evidence for electronic gap-driven metal-semiconductor transition in phase-change materials

Phase-change materials are functionally important materials that can be thermally interconverted between metallic (crystalline) and semiconducting (amorphous) phases on a very short time scale. Although the interconversion appears to involve a change in local atomic coordination numbers, the electronic basis for this process is still unclear. Here, we demonstrate that in a nearly vacancy-free binary GeSb system where we can drive the phase change both thermally and, as we discover, by pressure, the transformation into the amorphous phase is electronic in origin. Correlations between conductivity, total system energy, and local atomic coordination revealed by experiments and long time ab initio simulations show that the structural reorganization into the amorphous state is driven by opening of an energy gap in the electronic density of states. The electronic driving force behind the phase change has the potential to change the interconversion paradigm in this material class.