Featured Research

from universities, journals, and other organizations

Follow the ant trail for drug design: Ant behavior inspires software design

Date:
March 18, 2014
Source:
ETH Zurich
Summary:
New drugs often fail because they cause undesirable side effects. Researchers have now developed simulation software that predicts the properties of active agents and virtually builds new ones. The software's search process is modeled after the behavior of ants. In order to allow the software to search for new composite agents, the research team uses an ant algorithm. Like an ant colony on the search for food, the algorithm screens through the molecular building blocks for components with the desired properties. Depending on the strength of the desirable and undesirable effects of the virtual products, the building blocks receive a 'grade'. In the ant world, this would equate to marking the trail to food with pheromones.

The path to developing new drugs is a long one. If a target is identified for a new active agent -- for instance a particular protein that plays a key role in a disease -- an active molecule that binds to the target must then be developed. Pharmaceutical companies trawl through their collections of chemicals for substances that act on the target protein in the desired fashion.

However, these compounds are often just the starting point for a long process of adjustment and testing. Chemists use computer simulations to design new molecules to yield innovative compounds with the desired properties; however, undesirable effects often come to light only after the active agent has been synthesized and tested, and in the worst-case scenario only during the clinical trials.

To date, the prediction of side-effects using a computer has been limited. "Our aim is to detect problems as early as possible and synthesize only the most promising active agents," explains Gisbert Schneider, Professor of Computer-Assisted Drug Design at the Institute of Pharmaceutical Sciences, ETH Zurich. Many potential candidates that prove to have undesirable effects can thus be eliminated quickly.

Effective predictive module

Schneider's research team has developed a simulation module that can predict possible target activities of drug-like molecules more quickly and precisely than previous programs. The algorithm checks the interaction of a molecule with up to 640 human proteins in just a few minutes. "This is currently the most effective predictive module in existence," says Schneider. A trial run with a cholesterol lowering agent, fenofibrate, which has a range of side-effects, showed all known interactions with unintended targets as well as some previously unknown. Some of the unexplained side-effects of the drug could be attributed to the latter.

However, the computer module is capable of even more: it combines molecular building blocks from a virtual building set to suggest new chemical entities. It also checks the interactions of these with the 640 human proteins and suggests the best module combination.

Following the scent mark

In order to allow the software to search for new composite agents, the research team uses an ant algorithm. Like an ant colony on the search for food, the algorithm screens through the molecular building blocks for components with the desired properties. Depending on the strength of the desirable and undesirable effects of the virtual products, the building blocks receive a 'grade'. In the ant world, this would equate to marking the trail to food with pheromones.

In the next step, the components are recombined and the properties reassessed. In the process, a building block that received a high grade at the start can drop out of the short list, because it might has too many predicted adverse effects in combination with another building block. The 'scent mark' of the ant algorithm fades in this case, while the 'scent mark' for a better block combination is increased with every virtual combination step. In the end, the algorithm -- like the ants -- finds the quickest or best way to the goal by adaptive trial and error.

"Ant algorithms are used in robotics, for example for optimizing manufacturing processes, but we have now transferred the trick to drug discovery," says Schneider. As not only one ant but an entire colony of ants looks for the path -- in this case, numerous parallel and intercommunicating search processes -- the simulation module designs new active agents within minutes and suggests the necessary chemical synthesis steps. "What previously took up to two weeks can now be done in a day, thanks to the new software." In a next step, Schneider's team wants to connect the computer module to a synthesis robot to fully automate the design and subsequent synthesis.

According to Schneider, in future it may be possible to not only find the best active agent for a particular disease, but to develop medication for the individual patient. "If we could give the algorithm extra information, such as what the patient's protein world looks like, it could calculate the interactions to be expected for that particular patient." A suitable active substance could be selected and the patient treated with as few side-effects as possible.


Story Source:

The above story is based on materials provided by ETH Zurich. The original article was written by Angelika Jacobs. Note: Materials may be edited for content and length.


Journal References:

  1. D. Reker, T. Rodrigues, P. Schneider, G. Schneider. Identifying the macromolecular targets of de novo-designed chemical entities through self-organizing map consensus. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1320001111
  2. Michael Reutlinger, Tiago Rodrigues, Petra Schneider, Gisbert Schneider. Multi-Objective Molecular De Novo Design by Adaptive Fragment Prioritization. Angewandte Chemie International Edition, 2014; DOI: 10.1002/anie.201310864

Cite This Page:

ETH Zurich. "Follow the ant trail for drug design: Ant behavior inspires software design." ScienceDaily. ScienceDaily, 18 March 2014. <www.sciencedaily.com/releases/2014/03/140318112028.htm>.
ETH Zurich. (2014, March 18). Follow the ant trail for drug design: Ant behavior inspires software design. ScienceDaily. Retrieved September 18, 2014 from www.sciencedaily.com/releases/2014/03/140318112028.htm
ETH Zurich. "Follow the ant trail for drug design: Ant behavior inspires software design." ScienceDaily. www.sciencedaily.com/releases/2014/03/140318112028.htm (accessed September 18, 2014).

Share This



More Health & Medicine News

Thursday, September 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Artificial Sweetener Could Promote Diabetes

Artificial Sweetener Could Promote Diabetes

Newsy (Sep. 17, 2014) Doctors once thought artificial sweeteners lacked the health risks of sugar, but a new study says they can impact blood sugar levels the same way. Video provided by Newsy
Powered by NewsLook.com
Ebola Vaccine Trial Gets Underway at Oxford University

Ebola Vaccine Trial Gets Underway at Oxford University

AFP (Sep. 17, 2014) A healthy British volunteer is to become the first person to receive a new vaccine for the Ebola virus after US President Barack Obama called for action against the epidemic and warned it was "spiralling out of control." Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Obesity Rates Steady Even As Americans' Waistlines Expand

Obesity Rates Steady Even As Americans' Waistlines Expand

Newsy (Sep. 17, 2014) Researchers are puzzled as to why obesity rates remain relatively stable as average waistlines continue to expand. Video provided by Newsy
Powered by NewsLook.com
President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins