HIV - 1C70-Q1 - HIV protease

HIV
1C70-Q1
HIV protease

HIV protease is a recognised drug target. However, mutations of this protein render many of the inhibitors ineffective against mutant strains. This is one of several which are based on different crystal structures.

We expect this query to give above normal numbers of hits and higher than average job times on a typical PC.


P J Ala et al Biochemistry (1998) 37.43 p15042-9

50 billion molecules crunched

Find-a-drug has now crunched over 50 billion Molecules, 5 million Jobs

(that's 50 thousand million to our none english speakers who are using the long million)

Well done all.

Cancer - 1XBC-Q1 - Syk Tyrosine Kinase ( SYK )

Cancer
1XBC-Q1
Syk Tyrosine Kinase

Many Tyrosine Kinases including SYK are inhibited by some anti-cancer drugs. Tyrosine Kinases are also associated with rheumatoid arthritis, inflammation and immunological responses. A lack of selectivity might cause undesirable side-effects and prohibit long term use as preventative treatment. This query is based on a different crystal structure to 1xbb-q1.

We expect jobs for this query to give than typical numbers of hits in longer than average times.


S Atwell et al J Biol Chem (2004) 279 p55827-32

Keith Davies Interview by Team Hard Cider

Ars Technica : Team Hard Cider have posted an Interview with Keith Davies, the person in charge of Find-a-Drug.

DC.Ars: Team Hard Cider and Find-A-Drug
6/23/2005 8:59:21 PM, by Eric Bangeman

Cancer and HIV are two of the biggest killers worldwide. Both have treatments, many with nasty side-effects, but HIV and many types of cancer do not have a cure. With your help and the aid of modern technology, the Find-A-Drug project hopes to change that. In this issue of DC.Ars, we have an interview with Keith Davies, the project lead of Find-A-Drug.

Before we move on to the interview however, we’ll also point out that other diseases and ailments are also being targeted, including Multiple Sclerosis, Malaria, Diabetes and Tuberculosis. Ars Technica has a Find-A-Drug team named Team Hard Cider, which is team number 2167. THC is starting a two-week push, where many members of our other teams are running Find-A-Drug in an effort to boost the team. Any new members would be greatly appreciated!

Interview with Keith Davies
Ars Technica: What is Find-A-Drug?
Keith Davies: Find-a-Drug is a not-for-profit project which is funded by Treweren Consultants Ltd. It aims to find small drug-like molecules which can bind to proteins which are associated with specific diseases.
....

read more at Ars Technica

AntiBacterial - 1B70-Q1 - Phenylalanyl-tRNA synthetase

Proteome
1B70-Q1
Phenylalanyl-tRNA synthetase

Phenylalanyl-tRNA synthetase is an essential enzyme which catalyses the transfer of phenylalanine to the Phe-specific transfer RNA. Inhibitors of this enzyme have potential to be a new class of antibiotic which can be used against bacterial infection which do not respond to other antibiotics. This query is based on a different crystal structure to 1b7y-q2.

Some jobs for this query take longer than usual giving above average numbers of hits.

D Beyer et al Antimicrob Agents Chemother (2004) 48.2 p525-32

Cancer - 1XKK-Q1 - ErbB1 ( EGFR )

Cancer
1XKK-Q1
ErbB1

In cancer cells, the ErbB1 receptor tyrosine kinase (also known as EGFR) is sometimes present in higher concentrations than normal. ErbB1 (like ErbB2) is an important signally protein and stimulation leads to growth of the tumour. It may therefore be an important anti-cancer drug target.

We expect this queries to give many hits with job times longer than average.


E R Wood et al Cancer Res (2004) 64.18 p6652-9

HIV - 1NPV-Q1 - HIV protease

HIV
1NPV-Q1
HIV protease

HIV protease is a recognised drug target. However, mutations of this protein render many of the inhibitors ineffective against mutant strains.

We expect this query to give above normal numbers of hits and average job times on a typical PC.


P J Ala et al Biochemistry (1998) 37.43 p15042-9

New .biz server & A .com change

Server Changes

www.find-a-drug.com
Will be down until the server IP change gets updated around the web

Use www.find-a-drug.org and stats.find-a-drug.org.uk

New Server Added
www.find-a-drug.biz and stats.find-a-drug.biz
will also be available when the name gets updated around the web.

Extended Multiple Sclerosis Query - 1F45-Q3

Multiple Sclerosis Query 1F45-Q3, Human Interleukin-12B, has been extended.

Well as most people know and extended query is a positive thing, that's a who lot of molecules that are going to need crunching :-)

Alzheimers - 1U7T-Q1 - ABAD (aka HSD10 )

Proteome
1U7T-Q1
Amyloidβ-Peptide- Binding Alchohol Dehydrogenase (ABAD)

Amyloidβ-Peptide- Binding Alchohol Dehydrogenase (ABAD) is also known as 17β-hydroxysteroid dehydrogenase type 10 (HSD10). It has been implicated in the development of Alzheimer's disease. ABAD binds to βamyloid and plays a role in the neurotoxicity. An inhibitor which stops this binding might be useful therapeutically in the treatment of Alzheimers disease.

We expect most jobs for this query to take longer than average giving more hits than usual.


C R Kissinger et al J Mol Biol (2004) 342.3 p943-52

Cancer - 1Q2U-Q1 - DJ-1 / RS

Cancer
1Q2U-Q1
DJ-1/RS

DJ-1 is a protein involved in multiple physiological processes, including cancer, Parkinson's disease, and male fertility. The details of how DJ-1 functions are not known. In cancer it is believed that it reduces the levels of the PTEN tumour suppressor which enables cell growth.

We expect most jobs for this query to take less time than usual giving fewer hits.


Q Huai et al FEBS Lett (2003) 549 p171-5

Cancer - 1XBB-Q1 - SYK Tyrosine Kinase

Cancer
1XBB-Q1
SYK Tyrosine Kinase

Many Tyrosine Kinases including SYK are inhibited by some anti-cancer drugs. Tyrosine Kinases are also associated with rheumatoid arthritis, inflammation and immunological responses. A lack of selectivity might cause undesirable side-effects and prohibit long term use as preventative treatment.

We expect jobs for this query to give than typical numbers of hits in average times.


S Atwell et al J Biol Chem (2004) 279 p55827-32

1.30c beta released to testers

Find-a-Drug client v1.30c has been released to beta testers.

Clients should update automatically on their next receive.

Whats new

• A new command line option "-stop" has been implemented in 1.30c which stops the software until loader is run again. It takes up to 1 minute for THINK and SERVER to respond
• It is now possible to run more than one copy of server. This is intended for use under Linux when manual downloads of jobs and uploads of results can be executed without stopping the "main" copy.

What's fixed

• A problem with networked clients has been resolved in 1.30b providing members specify a username that has network access when the software is installed/configured for those clients.
• It is no longer necessary to specify as username and password (they weren't used anyway).
• If something went wrong starting up the software on a network client, it was not possible to display a message (no access to desktop) or write to the logfile (no local network access). Under 1.30c, the software attempts to send an e-mail as well as write to loader.log in the same folder as loader.exe.

Full list of v1.30 changes so far

Multiple Sclerosis - 1F45-Q3 - Human Interleukin-12B

Multiple Sclerosis
1F45-Q3
Human Interleukin-12B

Interleukin-12B (IL-12B) belongs to the cytokine class of proteins and is crucial for the generation of immunity to intracellular pathogens. It is known to stimulate production and enhance the activity of natural killer cells and T cells, and to induce production of interferon. It is important in preventing infection by intracelluar bacteria and parasites. IL-12B also contributes to various immunopathological conditions, so understanding its role may lead to new therapies for rheumatoid arthritis, multiple sclerosis and other autoimmune diseases. This query targets a variant of the site used in 1f42 -q2 .


C Yoon, S C Johnston, J Tang, M Stahl, J F Tobin and W S Somers Embo Journal 19 p3530 (2000)

Respiratory - 1MF7-Q3 - Integrin α M I domain

Third in the 1MF7 series

Respiratory Desease
1MF7-Q3
Integrin α M I domain

Integrin α M I domain is also known as Mac-1 is the receptor for MRP14 (see 1irj-q2). This receptor may mediate the membrane inflammaation response. This query targets a different binding site to 1mf7-q1.

Test jobs for this query gave more hits and took longer than typical jobs.


C J McCleverty and R C Liddington Biochem (2003) 372 p121

Anti Diabetic - 1A8I-Q1 - Glycogen phosphorylase

Proteome
1A8I-Q1
Glycogen phosphorylase

Glycogen phosphorylase is recognised as a potential antidiabetic target as it plays a role in metabolising glucose. At present, there are no collaborations in place to utilise these results and consequently this query is being processed as part of the proteome project. This query is based on a different crystal structures to 1h5u, 1b4d, 1c8l and 2gpa


N G Oikonomakos et al Bioorg Med Chem (2002) 10.5 p1313-9

Respiratory - 1MF7-Q1 - Integrin α M I domain

Respiratory Desease
1MF7-Q1
Integrin α M I domain

Integrin α M I domain is also known as Mac-1 is the receptor for MRP14 (see 1irj-q2). This receptor may mediate the membrane inflammaation response. This query targets a different binding site to 1mf7-q2.

Test jobs for this query gave more hits and took longer than typical jobs.


C J McCleverty and R C Liddington Biochem (2003) 372 p121

Malaria - 1BZY-Q1 - Hgprtase

Malaria
1BZY-Q1
Hgprtase

Hypoxanthine-Guanine Phosphoribosyltransferase (Hgprtase) is important as a source of purine to Plasmodium falciparum (the parasite which causes Malaria). This is because the parasite is unable to make its own purine. It has been suggested that inhibiting this enzyme may be therapeutically valuable. This query is based on a different crystal structure to 1d6n-q1.

In test jobs, this query gave more hits than usual with variable times.


G K Balendiran et al, Protein Sci (1999) 8.5 p1023

1.30c Delayed

Version 1.30c beta client has been delayed

THINK reported there has been a few problems with the current alpha version of 1.30c and these are mainly small, seems simple to implement idea's from the members

We hit some problems with the alpha test that is causing a slight delay - until next week.
We made the mistake of trying to implement a few simple suggestions and some of them - such as adding a service description didn't workout under Win9x!
There is a general simplification to service configuration, e-mailed error messages when the software can't display a pop-up message (eg from a hidden service), ability to run a second copy of server under Linux ... full details early next week.

Anti-Diabetic - 2GPA-Q1 - Glycogen phosphorylase

Proteome
2GPA-Q1
Glycogen phosphorylase

Glycogen phosphorylase is recognised as a potential antidiabetic target as it plays a role in metabolising glucose. At present, there are no collaborations in place to utilise these results and consequently this query is being processed as part of the proteome project. This query is based on a different crystal structures to 1h5u-q1, 1b4d-q1 and 1c8l.

The test jobs took slightly longer than typical jobs and have larger number of hits than average.


N G Oikonomakos et al Bioorg Med Chem (2002) 10.5 p1313-9

1M2R-Q1 - Extended Cancer Query

This query has been extended to a larger set of mollecules, this normally means the small set has been good and they want MORE! ;-)

Cancer
1M2R-Q1
Casein Kinase 2

Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. Casein Kinase 2 (CK2) is implicated in a variety of cellular functions and misfunctions. In tumours it is often present in abnormally higher concentrations, suggesting that inhibition may be of therapeutic value.

In tests, jobs took longer than typical jobs and gave more hits than usual.
They average around 16 to 24hrs per job for the first set


E De Moliner et al J Biol Chem (2003) 278.3 p1831-6

Cancer - 1P15-Q1 - Receptor Protein Tyrosine Phosphatase α

Cancer
1P15-Q1
Receptor Protein Tyrosine Phosphatase α

Receptor Protein Tyrosine Phosphatase α (RPTP-α) was suggested as a possible target for anti-cancer drugs in Drug Discovery Today (2005) 10.10 p735. However, as the family of vphosphatase is quite large, selectivity is likely to be important.

Test jobs ran slower than average jobs giving more hits.



E D Sonnenburg et al Biochemistry (2003) 42.26 p7904-14

Alzheimer's - 1XS7-Q1 - Beta-secretase (Memapsin 2)

Proteome
1XS7-Q1
Beta-secretase (Memapsin 2)

Beta-secretase is a recognised drug design target for Alzheimer's disease for which peptide inhibitors are already known. Such inhibitors are of little clinical use because of their high molecular mass. This query is based on a different crystal structure to 1fkn-q3 and 1m4h-q2.

L Hong et al Science (2000) 290 p150

Respiratory - 1MF7-Q2 - Integrin α M I domain

Respiratory Desease
1MF7-Q2
Integrin α M I domain

Integrin α M I domain is also known as Mac-1 is the receptor for MRP14 (see 1irj-q2). This receptor may mediate the membrane inflammaation response.

We expect this query to give variable numbers of hits with variable job times.


C J McCleverty and R C Liddington Biochem (2003) 372 p121

.org.uk Stats Server down - temp. fixed

The primary stats server seems to be down http://www.find-a-drug.org.uk/home1.html
Some of it works but the numbers parts don't.

The auto redirect will be altered if it doesn't come back to life.
It will be redirected to the still working backup server
http://stats.find-a-drug.com/

It maybe related to Denial-Of-Service type activity, like someone grabbing lots a molecule files or similar

Multiple Sclerosis - 1PKQ-Q4 - Myelin Oligodendrocyte Glycoprotein

Multiple Sclerosis
1PKQ-Q4
Myelin Oligodendrocyte Glycoprotein

Multiple sclerosis is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination, and nerve axon loss. The immune response is responsible for the degradation of the protective myelin sheath around the spinal cord. This involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG) located at the surface of CNS myelin. This is the third of a short series of queries where we seek small molecules which might inhibit the immune responsible which would halt the progress of the disease. The series target different sites of the same protein.

Test jobs for this query took less time than typical jobs giving few hits.


C Breithaupt et al Proc Nat Acad Sci (2003) 100 p9446

Alzheimer's - 1H4W-Q1 - Trypsin IV

Proteome
1H4W-Q1
Trypsin IV

Trypsin IV is a protease which is expressed in the brain. It has been suggested that this protein is linked to the formation of amyloid in the brain which is characteristic of Alzheimer's disease. A selective Trypsin IV inhibitor may be therapeutically useful to slow the development of Alzheimer's disease.

The test jobs times were variable with some jobs taking longer than average.


G Katona et al J Mol Biol (2002) 315.5 p1209-18

Diabetes - 1LQF-Q1 - Protein-Tyrosine Phosphatase 1B (PTP1B)

Proteome
1LQF-Q1
Protein-Tyrosine Phosphatase 1B (PTP1B)

It has been suggested that inhibitors of Protein-Tyrosine Phosphatse 1B (PTP1B) could be therapeutically beneficial in the treatment of type 2 diabetes. However, as there are many other phosphatases in the cell it is necessary to find selective inhibitors. Phosphatases have also been suggested as targets for other diseases.

The test jobs times were typical giving above normal numbers of hits.


E Asante-Appiah et al Biochemistry (2002) 41 p9043-51

HIV - 1BIU-Q1 - HIV Integrase

HIV
1BIU-Q1
HIV Integrase

HIV Integrase is considered a difficult target to inhibit. Merck have announced some success and this is part of a series of Integrase queries which attempt to find novel inhibitors. The other queries target alternative binding sites or are based on different crystal structures.

We expect jobs for this query to give below average numbers of hits with variable job times.


Y Goldgur et al, Proc Natl Acad Sci (1998) 95 p9150