Modelling magnetite biomineralisation : the interactions of proteins and Fe3O4 surfaces

• Main Author: Monnington, Amy Elizabeth
• Published: University of Huddersfield 2014
• Subjects: 572; QD Chemistry
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.638114

The biosynthesis of magnetite is the earliest known example of biomineralisation; how-ever, much of the detailed atomistic mechanisms by which the process occurs are unknown. Within the bacterial strain Magnetospirillum magneticum AMB-1, the formation of mag-netite nanoparticles is thought to occur under the influence of the Mms6 protein. The C–terminal of this protein is highly acidic, containing dense carboxyl and hydroxyl groups, and exhibits direct interaction with the magnetite surface. In this thesis, a novel atomistic model of Mms6-driven magnetite formation was developed and the interactions of amino acids, dipeptide, tetrapeptide and pentapeptide sequences, related to the C-terminus of Mms6, with the{100}and{111}magnetite surfaces (both in vacu and solvated) have been investigated. Each study was split into two systems; a classic molecular dynamics system and a constrained molecular dynamics system utilising the Potential of Mean Force. Initially, the attachment of the individual amino acids to magnetite surfaces was consid-ered. From these results, it was established that the {111} surface was the favoured for surface for amino acid attachment and bonding occurred through octahedral iron ions, rather than tetrahedral iron ions. Furthermore, the charged amino acids demonstrated a higher affinity for iron binding and solvation of unconstrained systems diminished the iron binding abilities of all the amino acids. Secondly, based on a glutamate repeat motif, the attachment of a series of di- and tetrapep-tides to the {100} and {111} magnetite surfaces was explored. It was hypothesised that if the negatively charged glutamate was substituted for a charge neutral alanine, the iron binding potential of the sequence would reduce. The results suggested that the substitu-tion of glutamate for alanine significantly reduces the iron binding affinity of the system on the {100} surface, irrespective of sequence length and composition. However, on the {111}surface, the introduction of alanine differentially modulates the iron binding activity of the sequences investigated. Sequential substitution in a two amino acid chain confers inhibition of iron binding, conversely, in a four amino acid chain, iron binding affinity is enhanced. The final chapter utilised pentapeptides taken from the Cterminal region, thus ensuring the full sequence was explored. The binding behaviour of these pentapeptides and their related mutants, were investigated. It was found that the different sections behaved differ-ently from each other, suggesting that the binding activity of the C-terminal sequence is partly dependent on how the amino acids interact with each other. It was theorised that sequence mutation would decrease iron binding; however, the data suggested that this was not always the case and was sequence dependent. Based on the constrained system data, mutation of the original sequences confirmed the hypothesis for DIESA, LRDAL and EVELR on the {100} surface, and for SRDIE and SDEEV on the {111} surface, whereas, the theory was contradicted for the counterparts surfaces and for both surfaces of ELRDA. This data also suggests that the {111} surface was the preferred surface of attachment, with the exception of LRDAL. For the unconstrained systems, the observations differed dependent on the data analysis technique utilised, as well as on the pentapeptide original sequence, with none of the sequences explored fully confirming the hypothesis. Furthermore, the presence of water in the unconstrained systems was detrimental to the iron binding potential of the pentapeptides. The data from both the unconstrained and constrained systems propose that, there are many factors affecting the iron binding ability other than sequence mutation, such as, surface type, iron type and sequence dependence.