Organisers

• Michael Allen (University of Warwick)
• Tiff Walsh (University of Warwick)

Supports

   CECAM

   ESF-SimBioMa

   EPSRC Materials Modelling Consortium

Description

The pioneering work of Stanley Brown [1] first showed that it was possible to identify, out of billions of possibilities, peptide sequences that could specifically bind to one inorganic material over a range of others. Since this influential paper was published, hundreds of similar experiments have been reported, publishing peptide sequences (aptamers) for recognising a range of inorganic materials (see the reviews of Refs [2,3] for examples) including metals, oxides and semi-conductors. At present, advances in experimental methods far outpace corresponding progress in theory and simulation in this emergent research area. Furthermore, although significant progress has been made in identifying sequences that possess specificity for a variety of targets, the underlying mechanisms of this specificity at the molecular level are at present unknown.

Recent experimental advances in aptamer selection techniques both in-vivo (phage-display, cell-surface display) and in-vitro (messengerRNA display) have opened up new vistas for combining biological and traditional materials via controlled interactions at the biointerface. Furthermore, advances in characterization techniques such as nuclear magnetic resonance (NMR), neutron reflectometry, surface-enhanced raman scattering (SERS), surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) are fast gathering pace in this area. Depite this, at present structural detail at the molecular level remains scarce for these biointerfaces. However, interpretation of these characterization experiments would be aided significantly if partnered with corresponding atomistic simulations of such biointerfaces. Furthermore, given that aptamer selection typically is taken from a limited and/or biased peptide library, there is ample scope for optimization of peptides via bioinformatics approaches that are based on 'scoring matrices' not yet fine-tuned for application to peptide-inorganic interfaces. Atomistic simulation data may conceivably be used in future to achieve this goal. In addition, very recent experiments [4] have revealed that aptamers can nucleate the inorganic materials that the peptides were initially selected against, opening the issue of how to simulate nucleation of inorganic material (such as biomineralization) in the presence of these peptides. The modelling of these biointerfaces should not be confined to the atomistic level alone. Very recent experimental work has revealed that multimers (e.g. trimers) of aptamers form regular, hierarchical nanoscale patterns when adsorbed onto the target inorganic surfaces against which the peptides were selected. This aggregation and patterning behaviour could be modelled using coarse-grained potentials, derived from atomistic simulations.

While the peptide/inorganic-surface interface is currently a 'hot topic' experimentally, and in principle amenable to study by simulation approaches, the meeting also has the broader remit of considering any type of biomolecule/inorganic-surface interface. This may include lipids and membranes, proteins, and pharmaceuticals in the biomolecule category. Target inorganics may encompass a range of models aside from flat surfaces, and cover shape effects ranging from surface steps and terraces to nanoparticle shape and size.

Scientific Objectives

The purpose of the workshop is to bring together experimentalists in this field with those working in simulation of biomolecule-inorganic interfaces, in order to exchange ideas and synthesize new ways forward for making maximising contact between theory and experimental characterization. It expected that progress will be made in devising/planning state-of-the-art advances in:

1. Force-field development: a key component of future biointerface simulations is the veracity of the force-field upon which such simulations are based. Although there are abundant force-fields for describing proteins, and similarly for inorganic materials, there are few force-fields that can adequately describe the interaction between the two components. Developments in this area will be a focus.




2. Simulation algorithms: the algorithms used to explore conformational space, in the presence of water (modelled explicitly or not) or other solvent, will be coupled to the model used to describe the interactions at the interface (i.e. the force-field). Methodologies of exploring conformational space (in the presence of solvent) are to be discussed.




3. Strategies for tackling larger length-scales: many experimental groups are now exploring nanoscale patterning/aggregation of macromolecules (based on their identified peptide sequences) on target surfaces. A priority will be the possible approaches (such as coarse-graining, coupled with apppropriate search algorithms, for predicting mesoscale patterning and aggregation.




4. Applications and Challenges: The peptides identified in experimental work are not mere curiosities, but have many, many possible applications ranging from construction of nanostructured optical and magnetic materials, to biosensor technology, to separation technologies and so on. Future use of modelling to advance such applications will be discussed. Advances in methods for calculating free energies at the biointerface will also be a priority. Progress and/or future work on modelling properties of biointerfaces (mechanical, electrical, transport, nucleation, etc) will also be addressed here.

References

[1] S. Brown Metal-recognition by repeating polypeptides, Nature Biotechnology 15 269 (1997)

[2] M. Sarikaya, C. Tamerler, A. K. -Y. Jen, K. Schulten and F. Baneyx Molecular biomimetics: nanotechnology through biology, Nature Materials 2 577 (2003)

[3] J. J. Gray The interaction of proteins with solid surfaces, Current Opinion in Structural Biology 14 110 (2004)

[4] H. X. Dai, W. S. Choe, C. K. Thai, M. Sarikaya, B. A. Traxler, F. Baneyx and D. T. Schwartz Nonequilibrium synthesis and assembly of hybrid inorganic-protein nanostructures using an engineered DNA binding protein, Journal of the American Chemical Society 127 15637 (2005)