Modelling of the interaction between peptides and graphitic surfaces

The aim of this thesis is to understand the interactions of peptides with graphitic surfaces such as carbon nanotubes and graphite, in order to help establish guiding principles for the design of peptide sequences with controllable affinity to graphitic surfaces. Atomistic molecular dynamics (MD) simulations with our extended polarisable AMOEBAPRO force-field, which includes parameters for graphitic surfaces is used throughout. The peptide sequences studied were identified by phage-display experiments for their strong affinity to CNTs, and are rich in tryptophan and histidine residues [94]. The importance of the tryptophan residues on the binding affinity to CNTs is investigated by mutating each tryptophan by either tyrosine and phenylalanine. In addition, the effect of the surface curvature on the binding affinity is also explored. It is found that sequences containing tryptophan residues have more affinity to graphitic surfaces than those containing tyrosine or phenylalanine. Furthermore, it is suggested that these peptide sequences were selected for interfacial shape, since in the case of graphite, a compromise between having all the aromatic residues close to the surface and also allowing the non-aromatic residues to approach the surface is found. Following this study, the interaction of peptide sequences with CNTs is again studied, but this time with the aim to investigate the order of the residues, on the binding affinity to CNTs. The influence of the peptide sequence on the binding affinity to CNTs is studied by scrambling the sequence (HWKHPWGAWDTL). This study suggests that binding affinity is strongly dependent on the order of the content of the peptide sequences and gives some useful insights to the identification of principles that may help in the design of peptide sequences with controllable binding affinity to CNTs. For instance, it is found that strong binding may be due to the presence of isolated pairs of tryptophans, while weaker binding may be due to the presence of two tryptophan residues intercalated by another residue. The interactions of water with graphitic surfaces – CNTs, fullerenes and graphite – are also considered and it is found that the water structuring at the interface is weak and that there are no more than tree layers of structured water on the graphitic surfaces. Finally, the effect of the presence of OH defects on CNTs on the binding affinity to peptides is investigated. The results show that the binding affinity is not significantly affected by the presence of OH defects, but a general increase in the peptide mobility is noticed, giving insights for the applications of real CNTs with peptides. The work described in this thesis helps to understand what are the key residues involved in the interaction with CNTs, why do these key residues bind better to CNTs and provide insights on the mechanisms of peptided binding to CNTs, by demonstrating the role of peptide conformation

Investigation of the influence of surface defects on peptide adsorption onto carbon nanotubes

The number of possible applications that interface carbon nanotubes with biological systems is rapidly growing, and with these advances comes a need for characterisation of such interfaces. Molecular simulation is one such approach, and many recent examples exist where simulation has been used to investigate the atomic-scale details of the interface between biomolecules and carbon nanotubes (CNTs). However, these studies have been confined to the realm of pristine CNTs. Here, we build on our previous work and use molecular simulation to consider the adsorption on to defective CNTs of peptide sequences known to bind to the CNT surface [Wang et al., Nat. Mater., 2003, 2, 196]. Two types of idealised chemical defects are considered, along with two different distributions of these defects on the CNT surface. We find that the densely-packed defect distribution yields relatively little engagement with the peptides. Spreading the defects out along the nanotube increases the degree of contact with the peptide, without affecting the binding strength of the peptide-CNT interface in most cases. Both types of defect tend to act more as physical barriers to peptide mobility than as a source of attractive interactions. The resulting physical confinement of the peptide did not affect all sequences in the same way; two of the four sequences were found to be more sensitive to the presence of defects. This study has implications for the practical usage of CNTs in a wide range of biological contexts, where well-dispersed, functionalised nanotubes are required

Modeling the binding affinity of peptides for graphitic surfaces. Influences of aromatic content and interfacial shape

Interactions between peptide sequences and graphitic surfaces-carbon nanotubes and graphite-are investigated using molecular dynamics simulations with a polarizable force-field. Peptide sequences selected to have a strong affinity for carbon nanotubes [Nat. Mater. 2003, 2, 196.] are rich in tryptophan. We investigate the importance of the tryptophan residue for two of these sequences by mutating each tryptophan with either tyrosine or phenylalanine. We find that, in line with recent experimental observations, the original, tryptophan-containing sequences support relatively stronger binding to both nanotubes and graphite, compared with the mutants. We ascribe this behavior to the additional structural stability conferred by the indole group at the interface. We also explore the effect of interfacial curvature on the binding affinity. Our findings suggest that these nanotube-binding peptides have also been selected for interfacial shape. For the graphite surface our results indicate a compromise exists between maintaining strong ring-surface interactions and allowing nonaromatic groups to also approach the surface

Atomistic modelling of the interaction between peptides and carbon nanotubes

Interactions between single-walled carbon nanotubes (SWNT) and peptides are investigated. An existing polarizable force field, using distributed multipoles up to quadrupoles for the electrostatics, is modified to include a description of the non-bonded interactions between a SWNT and peptides. Adsorption energies and structures calculated with this potential are compared with data from electronic structure theory. Simulations of binding and non-binding peptide aptamers, as identified from experiment, are shown to agree with current experimental observations

Modeling binding affinity at peptide-surface interfaces : the role of mutations

While many different peptide sequences have now been experimentally identified to have strong affinity for a huge range of materials, the question of why a given sequence binds so well while another does not remains to be properly answered. Use of molecular simluations is one of many complementary techniques that enables us to address these questions. In this contribution, a summary of our molecular simulation work in this area is presented. We have identified the crucial role of intra-peptide interactions in peptide-inorganic binding for both titania (below) and silica binders. We have also made a detailed investigation of the importance of tryptophan in nanotube-binding peptides via point mutations, and advance a hypothesis based on interfacial shape, explaining why aromatic residues might not dominate in graphite-binding peptides