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Development of a whole proteome platform to identify new therapeutic targets for noble gases (gaseome)

Development of a comprehensive in silico platform for the prediction and analysis of protein - noble gas interactions and potential therapeutic applications across the entire human proteome.

The noble gases represent an intriguing scientific paradox. They are extremely inert chemically but display a remarkable spectrum of clinically useful biological properties. Despite a relative paucity of knowledge of their mechanisms of action, some of the noble gases have been used successfully in the clinic, although this appreciation is relatively recent and the mechanisms responsible for biological activity are generally not well understood (Winkler et al., 2016). Air Liquide have an interest in understanding commercial, medical applications for the nobles gases specifically including a requirement to; a) Better understand the biological mechanisms of action of noble gases across the entire human proteome and; b) Exploit this information for the purpose of developing new therapeutic applications for noble gases. The latest Biosimulation approaches offer an opportunity to increase understanding of both aspects. Technologies offered by Moleculomics uniquely offer structurally-based open-ended lead discovery, toxicity screening and protein network identification that is completely unlimited in reach, applied across the entire proteome. Specific advances made by Moleculomics and of relevance to this project include; • An ability to accurately predict the structure of proteins using the latest homology methods in conjunction with threading, even in regions of low or remote homology, and for the vast majority of proteins across the whole human proteome which have yet to be crystallized • High throughput affinity docking using a range of different algorithms, consolidated using a consensus scoring approach • Automated characterization of binding pockets including the identification of residues involved in binding events • An interactive web based technology platform to facilitate high throughput analyses of protein-noble gas interactions and downstream therapeutic applications. Moleculomics is highly experienced in high throughput protein modeling and is currently working on the development of their flagship product Human3DProteome; a library of the 3D structures of every protein in the human body – a library of 30,000+ potential drug targets. Moleculomics are currently developing workflows to enable the high throughput screening of candidate small molecule compound(s) against the human proteome. Since Human3DProteome has been developed and validated using traditional small molecule compounds (drugs), it is not suitable for use with much smaller molecules and elements, such as the noble gases. This project is therefore a collaboration between Moleculomics Canada (a wholly owned subsidiary of Moleculomics UK with expertise in high throughput screening), Moleculomics UK (expertise in platform architecture, high throughput structural modeling and development of docking algorithms) and Air Liquide (definition of the molecular analysis specification, participation in testing program and the development of leads into commercial medical applications). The objectives of the project are to develop Human3DProteome such that it is able to reliably predict the interaction of the noble gases with the human body. This will facilitate the understanding of the mechanism(s) of action and potential medical applications of noble gases. The deliverables of this project will include; • An enhanced molecule analysis platform designed for use with the noble gases and validated against laboratory data found in the literature or from new dedicated experiments. • A database of molecular interactions to facilitate searching for interactions between the noble gases and the human body for the purpose of identifying high affinity “hits”. This represents an efficient down selection tool to assist the discovery of the most suitable starting place for laboratory work, potentially saving time and money whilst simultaneously improving the efficiency of R&D workflows.
Acronym: 
GASEOME
Project ID: 
11 704
Start date: 
01-05-2017
Project Duration: 
24months
Project costs: 
250 000.00€
Technological Area: 
Pharmaceutical Products / Drugs
Market Area: 
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