Automated design for drug discovery

December 12, 2012, University of Dundee

A system of 'automated design' for new drugs could help develop the complex therapies needed for many medical conditions while also improving drug safety and efficiency, new research from the University of Dundee has shown.

The 'Moneyball' approach taken by the research team utilises the principles of advanced statistical and data analysis which have seen to be increasingly influential in areas as varied as sport, finance and in forecasting the recent US Presidential election.

As more complex drugs are needed to treat more complicated problems - particularly in areas such as neuroscience, and cancer - the task facing and chemists is daunting. However, researchers at the College of Life Sciences at Dundee, in collaboration with partners in North America, have shown that an automated computational process analysing huge amounts of existing data could provide a valuable new tool in drug discovery.

The innovative approach taken by the research team mimics the creative process of human chemists, where are steadily improved through successive cycles of design and selection.

"One of the things that makes drug discovery so hard is that you're trying to improve several different properties at the same time," said Professor Andrew Hopkins, Chair of Medicinal Informatics at Dundee. "Evolution is a mechanism than can be applied to solving these kinds of optimisation problems, and the iterative process of adaption and selection of hundreds of thousand of possible solutions can be simulated in a computer.

"We have effectively proved the concept of automated design of new compounds, showing that by using algorithms to process massive amounts of data we can tackle problems of huge complexity. The system solves the design problem by using computational evolution to mimic the design process of human chemists but running it on a very large scale."

The research is published in the journal Nature.

Drugs have to be able to deliver their primary effects and not present adverse side effects or toxicity that render them unsafe. But for complex conditions drugs also have to be designed to hit multiple targets. Designing drugs to this kind of multi-target profile is a complex and exceedingly difficult task for medicinal chemistry.

Professor Hopkins and colleagues developed an automated adaptive design approach that can mimic the creative, iterative process of medicinal by using computational evolution of large numbers of compounds. They initially used it to look at an existing drug, Donepezil, which is used in treating Alzheimer's Disease.

"Professor Sir James Black, the Nobel Laureate and former Chancellor of the University, proposed that 'the most fruitful basis for the discovery of a new drug is to start with an old drug' and we followed that advice," said Professor Hopkins.

"We took the structure of Donepezil as a starting point and from there the system evolved its structure, computationally, over many generations to a variety of different profiles across a range of drug targets. The predicted profiles were then tested experimentally and we found that 75% of them were confirmed to be correct.

"This proof of concept shows that we could make significant advances in discovering and designing complex drugs, which could lead to improvements in safety and efficacy, while also potentially reducing the cost of , which is a high-risk and expensive process."

Professor Hopkins said improvements in data capture and management were key to developing the research.

"Just a few years ago this would not have been possible because we need the existing drug data to build on and it was not held in a way that it could be analysed like this. But there have been significant developments, aided by groups like ChEMBL in Cambridge, who are funded by The Wellcome Trust, in making drug design data available in a format computers can process. What we have found particularly exciting is the way the algorithm has been able to learn from the human experience of drug design and mimic it on a massive scale to solve complex design problems."

This phenomenon is reflected in the name of a new spin out company which has been formed to commercialise the technology – ex scientia – which is the Latin for "from knowledge".

Explore further: Scientist creates new cancer drug that is ten times more potent

Related Stories

Scientist creates new cancer drug that is ten times more potent

August 29, 2012
Legend has it that Ralph Waldo Emerson once said, "Build a better mousetrap, and the world will beat a path to your door." University of Missouri researchers are doing just that, but instead of building mousetraps, the scientists ...

3D structure opens new avenue for drug discovery

April 2, 2012
(PhysOrg.com) -- An international consortium has determined the structure of an important new drug target in complex with a synthetic molecule designed by our researchers, opening up new avenues for drug discovery.

New Moffitt Cancer Center patent promises to accelerate cancer trials

February 14, 2012
A new patent has been issued to Moffitt Cancer Center for a computerized system that efficiently selects the right patient for the right clinical trial. The newly patented system matches the registered patient's own molecular ...

Recommended for you

Opioid abuse leads to heroin use and a hepatitis C epidemic, researcher says

February 22, 2018
Heroin is worse than other drugs because people inject it much sooner, potentially resulting in increased risk of injection-related epidemics such as hepatitis C and HIV, a Keck School of Medicine of USC study shows.

Opioid addiction treatment behind bars reduced post-incarceration overdose deaths in RI

February 14, 2018
A treatment program for opioid addiction launched by the Rhode Island Department of Corrections was associated with a significant drop in post-incarceration drug overdose deaths and contributed to an overall drop in overdose ...

Heroin vaccine blocks lethal overdose

February 14, 2018
Scientists at The Scripps Research Institute (TSRI) have achieved a major milestone toward designing a safe and effective vaccine to both treat heroin addiction and block lethal overdose of the drug. Their research, published ...

Study shows NIH spent >$100 billion on basic science for new medicines

February 12, 2018
Federally funded research contributed to the science underlying all new medicines approved by the FDA over the past six years, according to a new study by Bentley University.

Opioid use increases risk of serious infections

February 12, 2018
Opioid users have a significantly increased risk of infections severe enough to require treatment at the hospital, such as pneumonia and meningitis, as compared to people who don't use opioids.

Placebo pills prescribed honestly help cancer survivors manage symptoms

February 9, 2018
Long after cancer treatment ends, many continue to deal with one particular symptom that refuses to go away: fatigue. In a new study, researchers at the University of Alabama at Birmingham and Harvard Medical School have ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Parsec
not rated yet Dec 12, 2012
Developments like this must drive dedicated creationists crazy. I mean if evolution works so well in the lab, it must be really hard to dismiss it as a force in nature.

At least it seems that way to me.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.