Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Map All Possible Drug-like Chemical Compounds

23.04.2013
Drug developers may have a new tool to search for more effective medications and new materials.

It's a computer algorithm that can model and catalogue the entire set of lightweight, carbon-containing molecules that chemists could feasibly create in a lab.

The small-molecule universe has more than 10^60 (that's 1 with 60 zeroes after it) chemical structures. Duke chemist David Beratan said that many of the world's problems have molecular solutions in this chemical space, whether it’s a cure for disease or a new material to capture sunlight.

But, he said, "The small-molecule universe is astronomical in size. When we search it for new molecular solutions, we are lost. We don't know which way to look."

To give synthetic chemists better directions in their molecular search, Beratan and his colleagues -- Duke chemist Weitao Yang, postdoctoral associates Aaron Virshup and Julia Contreras-Garcia, and University of Pittsburgh chemist Peter Wipf -- designed a new computer algorithm to map the small-molecule universe.

The map, developed with a National Institutes of Health P50 Center grant, tells scientists where the unexplored regions of the chemical space are and how to build structures to get there. A paper describing the algorithm and map appeared online in April in the Journal of the American Chemical Society.

The map helps chemists because they do not yet have the tools, time or money to synthesize all 10^60 compounds in the small-molecule universe. Synthetic chemists can only make a few hundred or a few thousand molecules at a time, so they have to carefully choose which compounds to build, Beratan said.

The scientists already have a digital library describing about a billion molecules found in the small-molecule universe, and they have synthesized about 100 million compounds over the course of human history, Beratan said. But these molecules are similar in structure and come from the same regions of the small-molecule universe.

It's the unexplored regions that could hold molecular solutions to some of the world's most vexing challenges, Beratan said.

To add diversity and explore new regions to the chemical space, Aaron Virshup developed a computer algorithm that built a virtual library of 9 million molecules with compounds representing every region of the small-molecule universe.

"The idea was to start with a simple molecule and make random changes, so you add a carbon, change a double bond to a single bond, add a nitrogen. By doing that over and over again, you can get to any molecule you can think of," Virshup said.

He programed the new algorithm to make small, random chemical changes to the structure of benzene and then to catalogue the new molecules it created based on where they fit into the map of the small-molecule universe. The challenge, Virshup said, came in identifying which new chemical compounds chemists could actually create in a lab.

Virshup sent his early drafts of the algorithm's newly constructed molecules to synthetic chemists who scribbled on them in red ink to show whether they were synthetically unstable or unrealistic. He then turned the criticisms into rules the algorithm had to follow so it would not make those types of compounds again.

"The rules kept us from getting lost in the chemical space," he said.

After ten iterations, the algorithm finally produced 9 million synthesizable molecules representing every region of the small-molecule universe, and it produced a map showing the regions of the chemical space where scientists have not yet synthesized any compounds.

"With the map, we can tell chemists, if you can synthesize a new molecule in this region of space, you have made a new type of compound," Virshup said. "It's an intellectual property issue. If you're in the blank spaces on our small molecule map, you're guaranteed to make something that isn't patented yet," he said.

The team has made the source code for the algorithm available online. The researchers said they hope scientists will use it to immediately start mining the unexplored regions of the small molecule universe for new chemical compounds.

The research was supported by a grant from the National Institutes of Health (P50-GM067082).

Citation: "Stochastic voyages into uncharted chemical space produce a representative library of all possible drug-like compounds." Virshup et. al. 2013. J. Am. Chem. Soc. [Epub ahead of print].

DOI: 10.1021/ja401184g

Ashley Yeager | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht The world's tiniest first responders
21.06.2018 | University of Southern California

nachricht A new toxin in Cholera bacteria discovered by scientists in Umeå
21.06.2018 | Schwedischer Forschungsrat - The Swedish Research Council

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Better model of water under extreme conditions could aid understanding of Earth's mantle

21.06.2018 | Earth Sciences

What are the effects of coral reef marine protected areas?

21.06.2018 | Life Sciences

The Janus head of the South Asian monsoon

21.06.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>