Platform for success
New in silico platform for antimicrobial development to meet the UK’s defence and security needs
Moleculomics, based in Swansea, in South Wales, has collaborated with the Defence Science and Technology Laboratory (Dstl) to produce an innovative new platform to assist in the development of novel antimicrobials.
This collaboration has led to the computational prediction of structures of entire bacterial genomes and the identification of homologous antimicrobial targets across a number of different organisms. The resulting computational platform, the first of its kind in the world, facilitates faster and more reliable antimicrobial development programmes.
The technology is based upon the ability of Moleculomics to accurately predict the 3D structure of the proteins of multiple bacterial genomes, including variant proteins (also known as resistance mutations). The resulting protein models are then applied to a High Throughput Screening process whereby each and every protein is screened against a set of 25,000 chemical compounds (which could be later developed into drugs) to assess the binding affinity between the protein and the drug.
This process was assisted by 1024 computer cores of HPC Wales, allowing for over 3 million affinity dockings with specific sets of biologically important and structurally notable proteins to be undertaken in a matter of weeks. Developed with input from Dstl, the resulting technology platform facilitates the addressing of questions driven by the scientific interests of the end users themselves. A significant capacity of this new technology is the ability to identify targets across a range of bacterial organisms for the potential development of broad spectrum antibacterials, as well as to identify common structural sites encoded by different genes in the same organism which will reduce the prospects of future antimicrobial resistance.
“The application of this novel tool advances the field of drug development through improved knowledge of protein-ligand interactions at enormous scale” Dr Richard Saint – Dstl Technical Partner
The project was originally funded by the Centre for Defence Enterprise (CDE) to facilitate the early stages of antimicrobial drug development and Dr Jonathan Mullins, Chairman of Moleculomics commented, “We are very fortunate to have secured this type of funding and to collaborate closely with exceptionally good and clear thinking
scientists at Dstl.” Moleculomics are currently translating the project’s core technology into a series of products aimed at both the pharma and bio-pharma markets. Dr Will Krawszik, Head of Operations at Moleculomics explained, “We are currently developing tools which will enable protein-ligand molecular interactions to be better understood for applications in both lead discovery and toxicity studies to assist the drug development process with higher quality targets whilst simultaneously identifying and eliminating problem compounds earlier in the R&D cycle.” It is expected that these tools will be available in the summer of 2015.
The above article was featured in issue 75, Spring 2015 edition, of the Welsh Government publication ‘Advances Wales’. The full publication can be found here.