Featured Research

from universities, journals, and other organizations

Computer simulations help predict effective drug candidates

Date:
April 21, 2014
Source:
Uppsala University
Summary:
Using computer simulations to predict which drug candidates offer the greatest potential has thus far not been very reliable, because both small drug-like molecules and the amino acids of proteins vary so much in their chemistry. Researchers have now cunningly managed to develop a method that has proven to be precise, reliable and general.

Using computer simulations to predict which drug candidates offer the greatest potential has thus far not been very reliable, because both small drug-like molecules and the amino acids of proteins vary so much in their chemistry. Uppsala researchers have now cunningly managed to develop a method that has proven to be precise, reliable and general.

The largest class of human target proteins for drugs are the so-called G-protein-coupled receptors. They are targets for about 40 per cent of all drugs on the market. These receptors are found in the cell membrane and handle the communication between the outside and the inside. When they react to external stimuli, by binding molecules, for example, a structural transformation takes place on the inside that triggers a signalling cascade (see 2012 Nobel Prize in Chemistry).

"In this way these receptors regulate our senses of smell, taste and vision as well as a number of other conditions and feelings," explains Professor Johan qvist, who directed the study, which is now being published in the journal PLoS Computational Biology.

Of the roughly 900 G-linked-protein receptors in humans, today we know the three-dimensional molecular structure of only about twenty. It is important to know this molecular structure when drugs are developed.

The method used today to understand how the receptors function is complicated and time-consuming. First the binding strength of series of molecules is measured (the binding of so-called agonists and antagonists). Then mutations are induced in the receptors in order to see how the binding properties are affected.

"This is both time-consuming and often difficult, because the genetically modified receptors have to be expressed in living cells. With our computational method, the mutation can be created in the computer, and the effect on receptor binding can be calculated with great precision," says Johan qvist.

The problem with this type of computer simulation has previously been that the amino acids of the proteins are so different, in terms of size, electrical charge, etc., which has presented problems in the calculations. But when the researchers divided the procedure into a long series of smaller computations, something happened -- suddenly they were getting exact and stable results.

The method has now been tested on a neuropeptide receptor and has been shown to be able to predict with great reliability both the effects of mutations and the receptor's ability to bind a series of different molecules. The method also makes it possible to determine whether a three-dimensional structural model of the molecules that are bound to each other is correct.

"The results are brilliant. We believe this has the potential to be extremely useful in drug research. It quite simply makes it easier and faster to find candidates for new drugs. The computational method is also so general that it can be used to study all sorts of other proteins bound to various types of functional molecules," says Johan qvist.


Story Source:

The above story is based on materials provided by Uppsala University. The original article was written by Anneli Waara. Note: Materials may be edited for content and length.


Journal Reference:

  1. Lars Boukharta, Hugo Gutirrez-de-Tern, Johan qvist. Computational Prediction of Alanine Scanning and Ligand Binding Energetics in G-Protein Coupled Receptors. PLoS Computational Biology, 2014; 10 (4): e1003585 DOI: 10.1371/journal.pcbi.1003585

Cite This Page:

Uppsala University. "Computer simulations help predict effective drug candidates." ScienceDaily. ScienceDaily, 21 April 2014. <www.sciencedaily.com/releases/2014/04/140421135928.htm>.
Uppsala University. (2014, April 21). Computer simulations help predict effective drug candidates. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2014/04/140421135928.htm
Uppsala University. "Computer simulations help predict effective drug candidates." ScienceDaily. www.sciencedaily.com/releases/2014/04/140421135928.htm (accessed August 22, 2014).

Share This




More Computers & Math News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Families Can Now Ask Twitter To Remove Photos Of Deceased

Families Can Now Ask Twitter To Remove Photos Of Deceased

Newsy (Aug. 20, 2014) In the wake of a high-profile harassment case, Twitter says family members can ask for photos of dying or dead relatives to be taken down. Video provided by Newsy
Powered by NewsLook.com
Ballmer Leaves Microsoft's Board, Has Advice For Nadella

Ballmer Leaves Microsoft's Board, Has Advice For Nadella

Newsy (Aug. 19, 2014) In a letter to Microsoft CEO Satya Nadella, Ballmer said he's leaving the board of directors and offered tips on how the company can be successful. Video provided by Newsy
Powered by NewsLook.com
What Google Can Gain From Special Accounts For Children

What Google Can Gain From Special Accounts For Children

Newsy (Aug. 19, 2014) Google will reportedly offer official accounts for children younger than 13 years old. Video provided by Newsy
Powered by NewsLook.com
Breakingviews: Ebola's Economic Impact Could Eclipse SARS

Breakingviews: Ebola's Economic Impact Could Eclipse SARS

Reuters - Business Video Online (Aug. 18, 2014) The virus ravaging Africa has yet to spread elsewhere. Yet Asia’s SARS crisis in 2003 showed how changes to behaviour can hurt the economy more than the actual disease, says Breakingviews' Una Galani. Video provided by Reuters
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