Characterisation of electron transport in bacterial nano-wire proteins through high performance computing and experimentation

Day to day life is increasingly reliant on electricity to support transport and communications in addition to the storage and preparation of food. This situation reflects rapid scientific developments since Alessandro Volta built the first battery just over 200 years ago. However electricity has been essential to humans, and indeed all forms of cellular life, ever since they have existed. This electricity arises from the electron transport chains underpinning the storage of solar energy in sugars during photosynthesis and the harnessing of the energy in sugars for cellular function, reproduction and motility during respiration. Specially designed proteins support electron transport during photosynthesis and respiration. Many of these proteins contain metal ions positioned at regular intervals within a polymer made of amino acids and we can immediately see parallels to the structures of the much larger cables and wires that move electrons in our mobile phones, toasters etc. The properties determining the flow of electrons through cables and wires are well established. However, the means by which a particular amino acid structure defines the rate of electron transfer within and between such proteins when dissolved in water is less well understood. Here we propose to provide insight into these mechanisms through a combination of computational and experimental methods. The subject of our study is an iron-containing protein, whose three-dimensional structure has been solved only a few months ago. This protein is a representative of a large family of structurally related, but functionally distinct, proteins that has been recognised only recently. These proteins allow microbes to colonise diverse and apparently inhospitable environments. They contribute to the operation of some microbial fuel-cells and to the virulence of numerous microbes capable of infecting humans and animals. By resolving the molecular details underpinning electron transport through these proteins we will provide fundamental insight into a wide-spread and important mechanism of biological electron transport. Some of the computational methods are already available and some of them need to be developed during the research programme. The new methodologies will be made available to other scientists for studying other proteins of interest. The knowledge gained will also provide the framework for developing proteins with bespoke electrical properties for use as molecular nano-wires in bioelectronic engineering.

The results of the research proposed will reach out to a diverse range of people and communities including

-academics interested in fundamental and applied studies of biological electron transport as detailed in the nature of the 'Academic
Beneficiaries'.

-those in the alternative energy sector with interests in exploiting multi-heme cytochromes as molecular 'wires' in mediatorless
biofuel cells.

-those in the industrial and public sector working in waste water purification and clean-up of radioactively contaminated water and soil

-those in the bionanotechnological industry aiming to develop novel bio-electronic communication tools between cells and inorganic materials and/or implantable bioelectronic devices

-industrial and academic users of the Car-Parrinello molecular dynamics software package (currently more than 6000 world-wide), benefitting from the code extensions proposed in the computational programme

These beneficiaries will be alerted to our findings by their timely presentation at conferences, in publications and through press-releases timed to coincide with the publication of our research in leading journals. They will also gain from access to the computational and biological resources generated during the project. We anticipate that this impact will begin to be realised from month 18 of the proposed programme of research through the activities of all of the research team. To highlight our research and its potential impact to these groups we will invite representatives to an international workshop on this topic in the second half of the grant period. This conference will bring together eminent speakers from academia and industry selected for their leading, international reputation in the area.

The work proposed will also shape the personal development of the two PDRAs. They will gain skills in either advancing computational methods and electronic structure theory or methods for characterisation of metalloproteins under the guidance of the PIs, Co-Is and collaborators. In addition, the synergistic nature of the research programme and regular meetings of the research team will ensure that the PDRAs gain an understanding of the complementary approaches being used to elucidate electron transfer kinetics. This, together with the multi-site nature of the project will ensure the PDRAs improve their skills in working collaboratively, and communicating effectively within and across sites. They will gain experience of project management under the guidance of the PIs who will also mentor their skills in oral, written and web-based communication of their findings. These impacts will begin at the outset of the project and continue to its completion.