Few weeks ago, I posted an entry on DNA origami. I thought the idea was neat and creative but little did I know there are already a lot of other stuffs going on in the world.
The field - Structural DNA Nanotechnology (SDN). The person - Paul Rathemund. He has two beautiful smiley faces on his website. Quoted from his Nature paper, "an obvious application of patterned DNA origami would be the creation of a 'nanobreadboard', to which diverse components could be added. The attachment of proteins, for example, might allow novel biological experiments.."
Just few days ago, I come across this exciting news - a group of scientists at Arizona State University's Biodesign Institute have developed the world's first gene detection platform made up entirely from self-assembled DNA nanostructures. This 'breakthrough' make possible a water soluble nanoarray which can help to build a more sensitive DNA probes.
Thursday, January 31, 2008
Wednesday, December 12, 2007
Secondary protein structure prediction
Secondary structure means?
In biochemistry and structural biology,secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids (DNA/RNA).
It does not, however, describe specific atomic positions in three-dimensional space, which are considered to be tertiary structure.
Protein Structure Prediction
-One of the most important goals pursued by bioinformatics and theoretical chemistry.
-Aim is to predict the three-dimensional structure of proteins from their amino acid sequences, sometimes including additional relevant information such as the structures of related proteins.
-It deals with the prediction of a protein’s tertiary structure from its primary structure.
-High importance in medicine (for example, in drug design) and biotechnology (for example, in the design of novel enzymes).
Some Examples of predictions are:
-Ab initio protein modelling
(Ab initio protein modelling methods seek to build three-dimensional protein models "from scratch", i.e., based on physical principles rather than (directly) on previously solved structures.)
-Comparative protein modelling
o Homology modelling (based on the reasonable assumption that two homologous proteins will share very similar structures.)
oProtein threading (scans the amino acid sequence of an unknown structure against a database of solved structures)
-Side Chain geometry prediction.
(Even structure prediction methods that are reasonably accurate for the peptide backbone often get the orientation and packing of the amino acid side chains wrong.
Methods that specifically address the problem of predicting side chain geometry include dead-end elimination and the self-consistent mean field method. Both discretize the continuously varying dihedral angles that determine a side chain's orientation relative to the backbone into a set of rotamers with fixed dihedral angles. The methods then attempt to identify the set of rotamers that minimize the model's overall energy. Rotamers are the side chain conformations with low energy. Such methods are most useful for analyzing the protein's hydrophobic core, where side chains are more closely packed; they have more difficulty addressing the looser constraints and higher flexibility of surface residues.)
In biochemistry and structural biology,secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids (DNA/RNA).
It does not, however, describe specific atomic positions in three-dimensional space, which are considered to be tertiary structure.
Protein Structure Prediction
-One of the most important goals pursued by bioinformatics and theoretical chemistry.
-Aim is to predict the three-dimensional structure of proteins from their amino acid sequences, sometimes including additional relevant information such as the structures of related proteins.
-It deals with the prediction of a protein’s tertiary structure from its primary structure.
-High importance in medicine (for example, in drug design) and biotechnology (for example, in the design of novel enzymes).
Some Examples of predictions are:
-Ab initio protein modelling
(Ab initio protein modelling methods seek to build three-dimensional protein models "from scratch", i.e., based on physical principles rather than (directly) on previously solved structures.)
-Comparative protein modelling
o Homology modelling (based on the reasonable assumption that two homologous proteins will share very similar structures.)
oProtein threading (scans the amino acid sequence of an unknown structure against a database of solved structures)
-Side Chain geometry prediction.
(Even structure prediction methods that are reasonably accurate for the peptide backbone often get the orientation and packing of the amino acid side chains wrong.
Methods that specifically address the problem of predicting side chain geometry include dead-end elimination and the self-consistent mean field method. Both discretize the continuously varying dihedral angles that determine a side chain's orientation relative to the backbone into a set of rotamers with fixed dihedral angles. The methods then attempt to identify the set of rotamers that minimize the model's overall energy. Rotamers are the side chain conformations with low energy. Such methods are most useful for analyzing the protein's hydrophobic core, where side chains are more closely packed; they have more difficulty addressing the looser constraints and higher flexibility of surface residues.)
MudPIT
Introduction
Before Multidimensional Protein Identification Technology (MudPIT) came about, Liquid Chromatography (LC) and Mass Spectrometry (MS) are used separately to fractionate and then identify protein composition from biological sample.
Disadvantage of using Liquid Chromatography
- Loss of material that commonly occurs in chromatographic processes
Disadvantage of using Mass Spectrometry (gel-based)
Although gel-based methods are widely used when it comes to the identification of protein, this method has several drawbacks:
- Problem identifying hydrophobic proteins
- Difficulty detecting low-level proteins (dye staining is not sensitive)
- Long experiment duration
- Inability to be automated
- Biological sample need to undergo solubilization
These problem decrease the sensitivity of the protein identification process and MudPIT seeks to address these problems by improving the separation and identification of proteins.
So what is MudPIT?
Multidimensional Protein Identification Technology, or MudPIT is a largely unbiased method for rapid and large-scale proteome analysis by multidimensional liquid chromatography, tandem mass spectrometry, and database searching by the SEQUEST algorithm.
Advantage of MudPIT
- Eliminate the problems of gel-based approach when it comes to MS
- More sensitive and thus able to detect low abundance proteins
- two-dimensional chromatography technique reduces sample loss
Workflow of MudPIT
1. Preparation of protein sample
2. Digest protein sample to peptides
3. Peptides are then seperated into two liquid column chromatography steps:
-strong cationic exchange
-reversed-phase high performance liquid chromatography (HPLC)
3. Acquire tandem mass spectra of peptide
4. Search mass spectra against a protein sequence database
5. Identification of protein in the sample using SEQUEST
source:
Technologies and Strategies for Reseach and Development
DRUG Discovery & Development
Before Multidimensional Protein Identification Technology (MudPIT) came about, Liquid Chromatography (LC) and Mass Spectrometry (MS) are used separately to fractionate and then identify protein composition from biological sample.
Disadvantage of using Liquid Chromatography
- Loss of material that commonly occurs in chromatographic processes
Disadvantage of using Mass Spectrometry (gel-based)
Although gel-based methods are widely used when it comes to the identification of protein, this method has several drawbacks:
- Problem identifying hydrophobic proteins
- Difficulty detecting low-level proteins (dye staining is not sensitive)
- Long experiment duration
- Inability to be automated
- Biological sample need to undergo solubilization
These problem decrease the sensitivity of the protein identification process and MudPIT seeks to address these problems by improving the separation and identification of proteins.
So what is MudPIT?
Multidimensional Protein Identification Technology, or MudPIT is a largely unbiased method for rapid and large-scale proteome analysis by multidimensional liquid chromatography, tandem mass spectrometry, and database searching by the SEQUEST algorithm.
Advantage of MudPIT
- Eliminate the problems of gel-based approach when it comes to MS
- More sensitive and thus able to detect low abundance proteins
- two-dimensional chromatography technique reduces sample loss
Workflow of MudPIT
1. Preparation of protein sample
2. Digest protein sample to peptides
3. Peptides are then seperated into two liquid column chromatography steps:
-strong cationic exchange
-reversed-phase high performance liquid chromatography (HPLC)
3. Acquire tandem mass spectra of peptide
4. Search mass spectra against a protein sequence database
5. Identification of protein in the sample using SEQUEST
Some projects using MudPIT:
1) Protein pathway and complex clustering of correlated mRNA and protein expression analyses in Saccharomyces cerevisiae
2)Food Standards Agency
This site is researching on the feasibility of using MudPIT as an alternative to gel-based approach for the rigorous safety assessment of GM plants.
3)Chloroplast proteomics: potentials and challenges
This is a site on botany research, this research is about the analysis of chloroplast proteome.
source:
Technologies and Strategies for Reseach and Development
DRUG Discovery & Development
http://www.hupo.org/educational/past_congresses/2007_seoul/3_MacCoss_color.pdf
Nature Publishing Group
posted by Alvin
Teritary Structure New Break Thru...
For Years.. Bioinformatician has been trying to solve the great mystery of the structure of a protein by prediction
In the past.. experts used to say.. To determining the shape of a protein!, is just a matter of firing X-ray Beam @_@ at its crystalline form and measure it... and!! chemists are way too sceptical to prove him WRONG!
Until recently .. recently...
Ah AH!! on 14/10/2007!~~ David Baker!,
A biochemist at Uni of Washington, and his colleagues found astonishing result! to prove what the experts sayd WRONG!!.. breaking the scepticism in the chemist's world!
Baker came out with a new techique, which combines information from the sum of
By : what is already known about the structure with the vast com - power available
{ what this means? => getting 150k of volunteers to use his program at home }
Soo.. how this program works?
In Basic :1) Breaks the protein sequence into small stretches
2) Match the stretches with all the known protein structures {Logically, if a result = very 100% = its also be 100% accurate}
3) minimize the free energy of the structure so to measure its stability!
4) Repeat all this steps Over and Over Again UNTIL! it lurch towards an ever more Accurate Protein Model!~ Woo{Theres too much data in the world of the web, so if they could get everything done, which will take quite sometime..result would be darn good.}
And this program is called....BOINC
So In full, Its like u take a sequence, with 112 amino acid protein for example,the Network will breakup it up into several million structures, "with some very long time"this Millions of structure will then be whittled down to 5{6 Zeros digit to 5... @_@!}
until 1 structure is found, it will then relate its structure with its determined structure frm its crytsal
But.. Even after this..., result might not be as precision as the cyrstal, BUT!least its good enough to "throw away" the X-ray techique.
Even so... theres still room for improvement,but for now.. the structure prediciton would be the prospect of custom-made proteins.which is used to hunt for sequence that correspond to the desired structures.
Now.. the team os currently redesigning the gp120 Protein of HIV,hoping to make a vaccine that could stimulate the immune system in a different wayfrom the nature of the virus,if this is possible.. "the reshaped protein should attack the virus more effectively then antibodies created"{If Success, i believe.. human, will no longer regard the danger HIV will cause, after all.. our heart contains 7 deadly sinson the other hand, innocent child, might be saved.... }
Baker's Words.."The days when protein modellers thoughtthey could make crystallization obsolete arelong gone"
“If you reallycare about the structure of your protein, youshould get some experimental data and combineit with modelling"
So, by the way things are progressing, "light" will soon be seem by us..
For more info : Rosetta@Home
For more info on Ppl helping out with BOINC : http://www.youtube.com/watch?v=GzATbET3g54
Bye Bye!
Post by Zhong En
In the past.. experts used to say.. To determining the shape of a protein!, is just a matter of firing X-ray Beam @_@ at its crystalline form and measure it... and!! chemists are way too sceptical to prove him WRONG!
Until recently .. recently...
Ah AH!! on 14/10/2007!~~ David Baker!,
A biochemist at Uni of Washington, and his colleagues found astonishing result! to prove what the experts sayd WRONG!!.. breaking the scepticism in the chemist's world!
Baker came out with a new techique, which combines information from the sum of
By : what is already known about the structure with the vast com - power available
{ what this means? => getting 150k of volunteers to use his program at home }
Soo.. how this program works?
In Basic :1) Breaks the protein sequence into small stretches
2) Match the stretches with all the known protein structures {Logically, if a result = very 100% = its also be 100% accurate}
3) minimize the free energy of the structure so to measure its stability!
4) Repeat all this steps Over and Over Again UNTIL! it lurch towards an ever more Accurate Protein Model!~ Woo{Theres too much data in the world of the web, so if they could get everything done, which will take quite sometime..result would be darn good.}
And this program is called....BOINC
So In full, Its like u take a sequence, with 112 amino acid protein for example,the Network will breakup it up into several million structures, "with some very long time"this Millions of structure will then be whittled down to 5{6 Zeros digit to 5... @_@!}
until 1 structure is found, it will then relate its structure with its determined structure frm its crytsal
But.. Even after this..., result might not be as precision as the cyrstal, BUT!least its good enough to "throw away" the X-ray techique.
Even so... theres still room for improvement,but for now.. the structure prediciton would be the prospect of custom-made proteins.which is used to hunt for sequence that correspond to the desired structures.
Now.. the team os currently redesigning the gp120 Protein of HIV,hoping to make a vaccine that could stimulate the immune system in a different wayfrom the nature of the virus,if this is possible.. "the reshaped protein should attack the virus more effectively then antibodies created"{If Success, i believe.. human, will no longer regard the danger HIV will cause, after all.. our heart contains 7 deadly sinson the other hand, innocent child, might be saved.... }
Baker's Words.."The days when protein modellers thoughtthey could make crystallization obsolete arelong gone"
“If you reallycare about the structure of your protein, youshould get some experimental data and combineit with modelling"
So, by the way things are progressing, "light" will soon be seem by us..
For more info : Rosetta@Home
For more info on Ppl helping out with BOINC : http://www.youtube.com/watch?v=GzATbET3g54
Bye Bye!
Post by Zhong En
Sunday, December 9, 2007
European Bioinformatics Institute (EBI)
About the Institute
An organisation which forms part of the European Molecular Biology Laboratory(EMBL).
- Provides research on bioinformatics
- Manage database of biological data
http://www.ebi.ac.uk/
About the Research groups
Having more than 25 groups at EBI, only abt 5 or more are research groups.
http://www.ebi.ac.uk/Groups/
An organisation which forms part of the European Molecular Biology Laboratory(EMBL).
- Provides research on bioinformatics
- Manage database of biological data
http://www.ebi.ac.uk/
About the Research groups
Having more than 25 groups at EBI, only abt 5 or more are research groups.
http://www.ebi.ac.uk/Groups/
Research group includes Bertone group, Luscombe group, Huber group, Thornton group and more.
Firstly, I ll talk about the Huber group, it's research focuses on the transcription of gene and the binding of protein and DNA with DNA microarray.
This group will provide aid in the understanding of functional genomics data.
The next group I ll talk about is the Luscombe group. Which focus on genomic analysis of regulatory system.
http://www.ebi.ac.uk/luscombe/
This group actually studies on how the biology of an organism look like by investigating on the cells of the different species, the expression of its gene, the production of protein, etc.
http://www.ebi.ac.uk/luscombe/research.html
Current status of the research:
- Provide graphical models for understanding the relationship of the regulatory network.
- Identifying the vulnerabilities of the regulatory network that is prone to diseases.
- How the transcriptional regulatory network interact with other cellular components.
- Analysing transcription factors in human genome.
- Complex bacteria behaviour
Future enhancements:
- Advancing analysis techniques and better understand regulatory network
- Consolidation of their research in bacteria and organism.
- Interacting with research groups performing genome-scale experiments.
Lastly, about Thornton group, they research on how biology works at molecular level, this has a very broad research.
http://www.ebi.ac.uk/Thornton/research.html
One of the many research in this group is the enzyme activity, which is study of how these enzymes work, their functions, and how they are evolved.
Current status of this research: http://www.ebi.ac.uk/Thornton/group_publications.html
Thursday, November 22, 2007
Ludwig Institute for Cancer Research
Ludwig Institute for Cancer Research So, what is Ludwig Institute for Cancer Research?
Who is the founder of this institute?
why does the founder want to set up this institute?
Well, Ludwig Institute for Cancer Research(LICR) is a non-profit organization which was set up in 1971 by the American business magnate Mr. Daniel K. Ludwig (the picture on the top right hand corner).
It’s aim is to control and destroy cancer by mastering it so as to relieve the human suffering caused by cancer.
Basically, LICR is the largest international academic institute with nine Branches in seven countries across Australasia, Europe, and North and South America, and numerous Affiliates in many other countries.
WOW.. LICR is going to set up its first Asian branch in Singapore
Just got to know that a new research centre will soon be opening in Singapore by the Ludwig Institute for Cancer Research (LICR). It is going to be the first Asia branch which collaborates with 3 Singapore institutions. A.STAR, YLL-NUS and Duke-NUS GMS.
This is going to be a world class laboratory research. LICR and Singapore is going to narrow the gap between the laboratory and the clinic and they hope to bring the research discoveries to human benefit.
You can read more about the news here: http://www.licr.org/C_news/archive.php/2007/11/04/ludwig-institute-for-cancer-research-to-set-up-its-first-asian-branch-in-singapore/
Immune system can drive cancers into dormant state
We know that the scientists have been working for years to make use of the immune system to get rid of cancers. This technique is known as the immunotherapy. But a new finding proves that, when the immune attack could not kill the cancer, the cancer will find all sorts of ways to contain itself in the immune system. This explains why some tumors seem to stop growing and go into a lasting period of dormancy.
You can read about the study in the following link: http://www.licr.org/C_news/archive.php/2007/11/19/immune-system-can-drive-cancers-into-dormant-state/
REF LINK: http://www.licr.org/
Genomics
Green Alga Genome Project
This is one of the interesting Genome Project that most people might be interested in. One of the significant alga is the "Chlamydomonas reinhardtii". It is known to the research community as Chlamy. It is uniquely associated with carbon dioxide capture and generation of biomass. As fossil fuel have their limitation in supply, biomass is getting more and more popular as it also produce lesser greenhouse gas emission when using appropriate agricultural techniques and processing strategies. Many functions of it associate with a human helps in the basic understanding of certain human diseases.
Source: http://www.jgi.doe.gov/News/news_10_11_07.html
Sea Urchin Genome Project
A species Purple Sea Urchin(Strongylocentrotus purpuratus) is known to be closely related to human as both of the species is under the kingdom of deuterostome. For example, the membrane-bound receptor guanylate cyclase implicated in the important human disease, heat-stable enterotoxin dysentery, was first isolated from sea urchin sperm.
Source: http://www.hgsc.bcm.tmc.edu/projects/seaurchin/
This is one of the interesting Genome Project that most people might be interested in. One of the significant alga is the "Chlamydomonas reinhardtii". It is known to the research community as Chlamy. It is uniquely associated with carbon dioxide capture and generation of biomass. As fossil fuel have their limitation in supply, biomass is getting more and more popular as it also produce lesser greenhouse gas emission when using appropriate agricultural techniques and processing strategies. Many functions of it associate with a human helps in the basic understanding of certain human diseases.
Source: http://www.jgi.doe.gov/News/news_10_11_07.html
Sea Urchin Genome Project
A species Purple Sea Urchin(Strongylocentrotus purpuratus) is known to be closely related to human as both of the species is under the kingdom of deuterostome. For example, the membrane-bound receptor guanylate cyclase implicated in the important human disease, heat-stable enterotoxin dysentery, was first isolated from sea urchin sperm.
Source: http://www.hgsc.bcm.tmc.edu/projects/seaurchin/
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