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

Abstract

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.

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

“…Although these studies demonstrate that polarizable MM FFs are able to provide reasonably accurate descriptions of the interaction properties of peptides on carbon substrates, such simulations are still computationally very demanding for the use of protein adsorption simulations. A viable approach is the inclusion of polarizability in graphene simulations via the rigid rod model, which was employed by Hughes et al (2014) to calculate the adsorption free energies of single amino acids on a aqueous graphene surface.…”

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

“…While this approximation can be understood from a practical point of view, a number of recent studies have shown that polarisation can influence the behaviour of the the graphitic-aqueous interfaces [45][46][47][48] as well as the interaction of biomolecules with such substrates, especially in the case of charged species. [49][50][51] One of the major challenges in incorporating polarisation effects into the FF is the increased computational cost. For example the AMOE-BAPRO FF is a high quality FF that accounts for the polarisation of atoms, but the computational cost associated with using it is high, 49,51 thus limiting the time-and/or length-scales of the simulation, and/or necessitating the use of an implicit solvent.…”

“…[49][50][51] One of the major challenges in incorporating polarisation effects into the FF is the increased computational cost. For example the AMOE-BAPRO FF is a high quality FF that accounts for the polarisation of atoms, but the computational cost associated with using it is high, 49,51 thus limiting the time-and/or length-scales of the simulation, and/or necessitating the use of an implicit solvent. 10,49,50,52 However, the use of an implicit solvent can bias the sampling of the system, promoting certain forms of secondary structure at the expense of others.…”

Force fields for simulating the interaction of surfaces with biological molecules

“…The GolP-CHARMM FF [43] mentioned previously incorporates polarization in a gold surface using a rotating rod model, retaining the fixed-charge description in the aqueous phase. Walsh and co-workers have also recently applied this method to silver [34] and graphite [39] surfaces, where they take advantage of the computational efficiency afforded by the fixed-charge treatment of the aqueous phase to calculate amino acid binding free energies.…”

“…We will cover three materials, gold, silica and polymers, because they are important for a range of biotechnological applications and they illustrate the primary concerns of FF development rsfs.royalsocietypublishing.org Interface Focus 6: 20150045 such as parameter balance and validation, but there is ongoing work on FFs for other materials like metals [33,34], metal oxides [35], minerals [36,37] and graphene [38,39].…”