Computer based drug Discovery // Drug Repurposing

Computer based drug Discovery

As an Associate Principle Scientist at the Oncology Innovative Medicines unit at AstraZeneca, my job involves using computer modelling of molecules and proteins to design new drug-like compounds and predict their properties for a diverse range of cancer targets. Over the last 10 years I have witnessed first-hand the increasingly valuable role our work plays within the organisation. In that time computational chemistry has become deeply embedded within the broader research teams and we collaborate closely with drug designers and other disciplines on a daily basis. These are exciting times – computer-aided drug design is now an integral part of the programme at AstraZeneca and we have access to enormous computing power through our scientific high-performance computing infrastructure.

Although we are playing an increasingly visible role in the drug discovery process, we appreciate that to some, our work may remain somewhat of a mystery. So we would like to pull back the curtain and offer you a glimpse into what could be a typical day in the life of a computational chemist where you can see how we have an impact across the drug discovery process…

* First thing today, I’m using protein structure information to assess a group of protein targets – I’ll pass on my findings to the Target Selection team.

* After that, it’s time to deal with the results of our recent High-Throughput Screen (HTS) – a million compounds – using clustering, statistical techniques and predicted selectivity to select about 10, 000 hit compounds for follow-up screening (You can read more about HTS in a previous blog entry here).

* Mid-morning – time for a coffee and then some Virtual Screening (VS). I’m using molecular shape and pharmacophore similarity to select around 1, 000 from 10 million commercially available compounds, to supplement the HTS screening hits.

* After lunch and I’m performing some Compound Docking with the new protein structure to see how the best compounds bind to the target protein. I’ve also mapped the interaction points within the binding site and I plan to design a set of new compounds that will incorporate new interactions and hopefully lead to a tool compound for our biologists.

* Straight after that we have a Design Team meeting to discuss and prioritise new ideas with the chemists and lead designers. We organise all our ideas using our in-house collaboration tool – Design Tracker. Team work is critical in drug-design – you can find out more about the initial work that led to the creation of Design Tracker .

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An anecdotal response

by invivoVibrio

I have worked in several labs that have produced, either directly or through a spin-off company, real products that are medically useful. Scientists are the ones who create vaccines, design diagnostic devices and tests, and discover useful drugs.
There's a whole spectrum that falls under the title "science," which ranges from the purely discovery-oriented, focusing on just learning more about a topic for learning's sake; to the purely practical, such as so-called translational research, where scientists iron out the details of a practically useful discovery and optimize it for practical applications, "translating" the basic science into something that can be produced and sold by industry

Springer Structure-based Drug Discovery
Book (Springer)

Cancer-Fighting Patch to Treat Mouth Cancer  — Drug Discovery & Development
Ohio State, through the Ohio State Innovation Foundation and the university's Drug Development Institute, and the University of Michigan licensed the intellectual property to the newly formed Sirona Therapeutics.

Springer Fragment-Based Drug Discovery and X-Ray Crystallography (Topics in Current Chemistry, Vol. 317)
Book (Springer)
Royal Society of Chemistry Structure-Based Drug Discovery: An Overview (RSC Biomolecular Sciences)
Book (Royal Society of Chemistry)
American Chemical Society Library Design, Search Methods, and Applications of Fragment-Based Drug Design (Acs Symposium Series)
Book (American Chemical Society)
Academic Press Structural and Mechanistic Enzymology:, Volume 87: Bringing Together Experiments and Computing (Advances in Protein Chemistry)
Book (Academic Press)