Featured Research

from universities, journals, and other organizations

Improved method for protein sequence comparisons is faster, more accurate, more sensitive

Date:
January 15, 2012
Source:
Ludwig-Maximilians-Universität München
Summary:
Sequence comparisons are an essential tool for the prediction and analysis of the structure and functions of proteins. A new method developed by computational biologists permits sequence comparisons to be performed faster and more accurately than ever before.

Lightning fast and yet highly sensitive: HHblits is a new software tool for protein research which promises to significantly improve the functional analysis of proteins. A team of computational biologists led by Dr. Johannes Söding of LMU's Genzentrum has developed a new sequence search method to identify proteins with similar sequences in databases that is faster and can discover twice as many evolutionarily related proteins as previous methods. From the functional and structural properties of the identified proteins conclusions can then be drawn on the properties of the protein to be analysed.

Related Articles


"Our method will expand the scope and power of sequence analysis, which will in turn facilitate the experimental elucidation of the structure and function of many proteins," says Söding, who is also a member of the Center for Integrated Protein Science Munich (CiPSM).

Proteins are involved in nearly all biochemical processes of life. The functions that a protein performs largely depend on the sequence of the 20 amino acid building blocks and on the three-dimensional spatial structure into which this sequence of amino acids folds. From the similarity of protein sequences, bioinformatic methods can predict their evolutionary relatedness, which in turn implies similar structure and functions. Therefore, proteins to be studied are standardly subjected to a sequence search, in which their sequence is compared with millions of sequences in public databases with annotated structures and functions. The properties of the protein of interest can then be inferred from the properties of the proteins with similar sequences, including its structure and functions. The general relationship between sequence and function makes it possible to predict the structure and function of a given protein by comparing its sequence with those of proteins of known structure/function. Publicly accessible databases exist in which the sequences of known proteins are stored, together with information on their biological functions, which facilitates such comparisons. "This kind of sequence analysis is a fundamental tool in the field of bioinformatics," explains Söding.

The sequence search programs assess sequence similarity by computing pairwise alignments: the two sequences of amino acids are arranged one above the other in such a way that mostly identical or similar amino acids are paired up in the same columns. "Perhaps even more important than the search for pairwise sequence similarities is the assembly of so-called multiple sequence alignments; in this case one searches for similar sequences in many related proteins and arranges them into a matrix, in which each sequence fills a row and similar amino acids end up in the same columns" says Söding. Because the functions and structure of evolutionarily related proteins are generally conserved -- i.e. preserved even when the sequence is altered by mutations during the course of evolution -- multiple sequence alignments form the basis for the prediction of the structure and molecular functions of uncharacterized proteins.

For the past 15 years, the program PSI-BLAST has been the most popular tool for the comparison of protein sequences, as it combines speed with high sensitivity and precision. Now Söding's team has designed a method, called HHblits, which clearly surpasses PSI-BLAST in all aspects of performance. This improvement is largely due to two factors. First the researchers convert both the sequence of interest and the sequences in the database to be searched into so-called Hidden Markov Models (HMMs). HMMs are statistical models that incorporate the mutation probabilities determined from sequence alignments -- so this step increases the sensitivity and precision of the subsequent similarity search. In addition, the team has developed a filtering procedure that allows them to reduce the amount of data that needs to be searched without appreciable loss of sensitivity. The trick is first to assemble similar sequences from the database into multiple sequence alignments. Each alignment column is then labeled with one of 219 "letters," such that columns with similar amino acid composition are represented by the same letter.

"By translating the multiple sequence alignments into sequences composed of these 219 letters, we can replace the time-consuming pairwise comparison of HMMs by the comparison of simple sequences," says Söding. This reduces the search time 2500-fold. Söding emphasizes that "HHblits allows to predict the function and structure of proteins more often and more accurately than was previously possible." His group is already working on further improvements to the method, for example by incorporating information on the three-dimensional structures of proteins.



Story Source:

The above story is based on materials provided by Ludwig-Maximilians-Universität München. Note: Materials may be edited for content and length.


Journal Reference:

  1. Michael Remmert, Andreas Biegert, Andreas Hauser, Johannes Söding. HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nature Methods, 2011; DOI: 10.1038/nmeth.1818

Cite This Page:

Ludwig-Maximilians-Universität München. "Improved method for protein sequence comparisons is faster, more accurate, more sensitive." ScienceDaily. ScienceDaily, 15 January 2012. <www.sciencedaily.com/releases/2011/12/111225194725.htm>.
Ludwig-Maximilians-Universität München. (2012, January 15). Improved method for protein sequence comparisons is faster, more accurate, more sensitive. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2011/12/111225194725.htm
Ludwig-Maximilians-Universität München. "Improved method for protein sequence comparisons is faster, more accurate, more sensitive." ScienceDaily. www.sciencedaily.com/releases/2011/12/111225194725.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) — It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) — More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) — In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) — A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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