Cloud-based methods to predict the druggability of protein-protein interactions: applications to cancer and antimicrobial resistance.

Lead Research Organisation: University of Nottingham
Department Name: Sch of Pharmacy

Abstract

Computational simulations allow us to make predictions about how biological molecules interact with (stick to) each other, and how these interactions, if they go wrong, can lead to disease. If this is understood then there is the potential to design new drugs that prevent this unwanted interaction between the protein molecules, and so treat the disease. This approach has great potential in areas as diverse as cancer therapy and new antibiotics. The problem is that the computer simulations needed for this type of study are enormous - typically they require access to the world's largest supercomputers. However, new research has shown how the same type of simulation study can be accomplished by spreading the work over very large numbers of smaller computers which may be spread all around the world. Such computer facilities - "the cloud" - are already incredibly important in fields ranging from business to social media, but the idea hasn't yet really made an impact in computational medical science. Our aim is to help this happen.
Building on years of previous experience developing computer software to help biological scientists and chemists easily use supercomputers for their research, we will develop a toolkit for "cloud-based computational chemistry". This will make it possible for far more researchers, all round the world, to do the same sort of cutting-edge medical research that until now was only possible for those groups who could access a supercomputer. We will test the power of this new facility by using it to study two particular diseases - cancer and antibiotic resistance. In both cases we will build on the research experience and interests of our industrial partner, the pharmaceutical company UCB Celltech. This ensures that, should we get some promising results, the theoretical predictions can quickly be tested in the lab, and if they hold up, taken forward into the development of new drugs for these key health problems.

Planned Impact

Who might benefit from this research?

This research aims to improve our ability to design new drugs: both new drugs for new targets, and better drugs for established targets. It could therefore benefit the general public and the UK economy.

How might they benefit?

New medicines could be developed to treat diseases that so far have been difficult to tackle, or new medicines could be developed that are more effective than existing ones, maybe due to fewer side effects.
The UK pharmaceutical industry is a major part of the UK economy. New drugs and medicines would give them a competitive advantage and could provide new employment opportunities.

Publications

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Title Crossbow - a cloud platform for computational chemistry 
Description Xbow allows you to create your own custom compute cluster in the cloud. The cluster has a "head' node that you communicate with and can log in to, a number of 'worker' nodes to run your jobs, and a shared file system that links them all together. Currently Xbow focusses on supporting the Biomolecular Simulation community, but is potentially useful in any field. 
Type Of Technology Software 
Year Produced 2018 
Open Source License? Yes  
Impact Computational chemists in two SMEs (UCB and NovaData Solutions) are engaged with us to see how the software can be used to aid their activities. 
URL https://github.com/ChrisSuess/Project-Xbow/tree/master/xbow
 
Description Joint BioExcel/MolSSI workshop on workflows in boimolecular simulation 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Co-organised with BioExcel and MolSSI a workshop (https://bioexcel.eu/events/bioexcel-molssi-workshop-on-workflows-in-biomolecular-simulations/) bringing together practitioners from across Europe and the US who are developing software tools that support workflows in bimolecular simulation, with the aim of sharing best practice, and opportunities for harmonisation and developing a model for sustainable development and broad community engagement. The event attracted 20+ representatives from across Europe and the US, and involved two key community development organisations, BioExcel (https://bioexcel.eu) and MolSSI (https://molssi.org).
Year(s) Of Engagement Activity 2018
URL https://bioexcel.eu/events/bioexcel-molssi-workshop-on-workflows-in-biomolecular-simulations/