Power Supply Interuptions

They had some power supply interuptions late last night (29th Sept)

So if you notice any stats problems please inform support, but leave it a day or two to see if it sorts itself out.

Cancer - 1B8Y-Q1 - Stromelysin

Cancer
1B8Y-Q1
Stromelysin

Stromelysin belongs to the class of Matrix MetallogProteinases (MMPs). It is a recognised anti-cancer target which is associated with tumour blood supply although finding clinically effective molecules has proven difficult.

The job times for test queries varied often giving above average numbers of hits.


R C Rizzo et al J Med Chem (2004) 47.12 p3065-74

Methodology - 1H9Z-Q1 - Serum Albumin

Methodology
1H9Z-Q1
Serum Albumin

Serum albumin is an important transport protein in the blood playing a key role in the transport of fatty acids, metabolites, and some drugs. However, one might expect undesirable side-effects from molecules which bind strongly. In addition, such molecules are likely to show exceptional pharmacokinetics with abnormally long retention times in the body. This query is based on an alternative site in a different protein crystal structure to 1e7a-q1.

This query gave above average numbers of hits and job times

I Petitpas et al J Biol Chem (2001) 276 p22804

Extended Query - Cancer - 1EV2-Q2

Cancer Query 1EV2-Q2 Fibroblast Growth Factor Receptor-2 has been extended into a larger molecule set.


Since this has been extended you can get a good idea of how it will hit and how long it will take to complete a job by looking at the below information

Tuberculosis - 1W2G-Q1 - Thymidylate Kinase (TMPK)

Respiratory Diseases
1W2G-Q1
Thymidylate Kinase ( TMPK )

This kinase converts thymidine monophosphate (TMP) to the di- and tri-phosphates. Inhibiting this process would be expected to significantly disrupt the cell cycle (ie growth). There is sufficient variation from the mammalian form and that found in mycobacterium tuberculosis to give scope for selective inhibition. This query is based a different crystal structure to 1g3u-q1.

In test jobs, this query took less time than typical jobs and gave below average numbers of hits.


I Li de la Sierra et al J Mol Biol (2001) 311 p87-100

Antibacterial- 1AJ6-Q1 - Gyrase B

Proteome
1AJ6-Q1
Gyrase B

Gyrase is a recognised antibacterial target. However, existing inhibitors have not had therpeutic potential because of serious side-effects and mutant resistance. It may be possible to find alternative inhibitors which do not have these limitations.

Job times for this query took less time than typical jobs giving below average numbers of hits.

A Tanitame et al J Med Chem (2004) 47.14 p3693-6

Insider Update from THINK

THINK has given a short update of how things are going, status of the new client and their current priorities. Also mentioned is hopefully some good news.

• Confirmation of cancer hits, new certificates soon
• Collaborations old and new are highest priority
• A jump in client version possible, but is of lower priority

Quote THINK

We have some further confirmation of cancer hits and we anticipate some more certificates to be available in a month or so.

We are also endeavouring to work closely with our collaborators to help progress their research. Supporting our existing collaborations and seeking further collaborations is our current priority. While we are making some progress on further collaborations we need to find more resources to keep up with the rate of processing queries.

In other words, we have deliberated lowered the priority of software development and this will mean that some cosmetic issues slip down the priority list. We appreciate that this will be more apparent to members than computational issues but we believe the decision is the correct one. We will make a decision later this month whether to take 1.30d to beta test or jump to 1.31.

EDIT to add

Quote more from THINK

Perhaps I should re-iterate that in general we do not have collaborations in place for Proteome and Methodology queries. However, interest has been shown in some of the Proteome queries and results have been made available to collaborators.

Validation studies have shown that 10-30% of the hits usually show the predicted biological activity in laboratory tests. We also see exceptions to these normals (for instance in anti-cancer tests) which are explained by a misunderstanding of where the molecule needs to bind or the role of the protein.

In recently, the investment in drug discovery has decreased to release more funds for drug development - especially in the smaller biotechs and pharmaceuticals. An associated trend in the industry is a shift to collaboration and licensing agreements for molecules which have progressed into development - ideally through phase 1 clinical trials. The interest in licencing hits discovered or molecules which show the desired activity in laboratory tests has decreased. IMHO this is why some DC projects (such as UD/Oxford/Inhibox) have not yet achieved the expectations they set.

Academic collaboration potential is unchanged but generally progresses slower than industrial drug research. Finding more collaborators and supporting/laising with existing ones is time-consuming.

18 Queries Closing - on 22nd October

On the 22nd October 2005 the following 18 queries will be closing to new results.

1AAP-Q2 1YVJ-Q1 1A2N-Q1 1NPW-Q3 2MBR-Q1 1EVT-Q1
1YBG-Q1 1PBQ-Q1 1AM6-Q2 4ERK-Q1 1NBU-Q1 1E7A-Q1
1SB8-Q1 1FX9-Q1 1YCJ-Q1 1YCA-Q1 1PME-Q1 1UTT-Q1


Unless they get extended of course. So if you have them in your queue, finish any that are running and remove the rest, though normally you will have long finished any of these jobs.

Cancer - 1PQ1-Q3 - BCL-XL

Cancer
1PQ1-Q3
BCL-XL

BCL-XL plays a role which is not fully understood in stimulating cell death. It is a recognised target for anti-cancer drugs. This query targets a different site on the same protein as 1pq1-q2.

The times for test jobs of this query were variable but usually taking less time than average jobs and often giving few hits.


X Liu et al Immunity (2003) 19.3 p341-52

Alzheimer - 1TL9-Q1 - Calpain

Proteome
1TL9-Q1
Calpain

Certain neurodegenerative conditions are associated with damage to the nerve axons or termini. It has been reported that Calpain inhibitors offer some protection to such nerve damage. Such inhibitors may have potential as drugs in autoimmune and other neurodegenerative diseases. This query is based on a different crystal structure to 1nx3-q1.

These jobs take longer than most typical jobs giving average numbers of hits.


G M O Hanlon et al Brain (2003) 126.11 p2497-2509

Cancer - 1UOM-Q1 - Estrogen-α Receptor

Cancer
1UOM-Q1
Estrogen-α Receptor

The estrogen receptor belongs to the family of Nuclear Receptors which trigger protein synthesis (via DNA transcription). Hormones bind to the ligand binding domain facilitating the DNA to interact with another domain. Inhibiting the Estrogen ligand binding domain is thought to have potential in cancer therapy. This query is based on a different crystal structure to 1sj0-q1.

This query gave more hits than typical jobs with jobs taking longer than average.


S Kim et al, J Med Chem (2004) 47.9 p2171-5

Diabetes - 1M2Z-Q1 - Glucocorticoid Receptor

Proteome
1M2Z-Q1
Glucocorticoid Receptor

The Glucocorticoid receptor has been suggested as a target for type II Diabetes. However, any inhibitor would need to be selective to receptors in the liver in order to reduce glucose production without side-effects.

This query gave fewer hits than typical jobs taking less time than average.


T W von Geldern et al, J Med Chem (2004) 47.17 p4213-30

New Server to Accept Results

find-a-drug.biz is now configured to accept results.

The software will automatically update cgi.lis (on its next connection to Find-a-Drug) and continue to work without user intervention.

That now makes it three servers now able to accept results, the two others being find-a-drug.org.uk and find-a-drug.net

Stats Problem and Tests

Problems
The stats server's have been having a few troubles recently with the odd update not working.
These should hopefully have been fixed by the time you read this.

Note totals may not tally at the moment but no results have been lost, says THINK.

So wait a few days then check again
Also results for 1pq1-q2 were not being processed yesterday but should have been done today if they get time.


Testing ( to quote THINK )

We are testing code to take the team and country identifiers from the most recently changed installation with the Nickname and E-mail address rather than the most recent installation. This should reduce inconvenience for members and alleviate the support load.

Members are advised to continue to make changes in all their installations as otherwise they may inadvertently revert to membership of an old team by pushing the Save button on an installation which is configured for the old team.

Alzheimers - 1QKM-Q1 - Estrogen-β Receptor

Proteome
1QKM-Q1
Estrogen-β receptor

The estrogen receptor belongs to the family of Nuclear Receptors which trigger protein synthesis (via DNA transcription). It has been suggested that stimulating the Estrogen-β receptor in the brain might be therapeutically useful in the treatment of Alzheimer's disease. Inhibiting the Estrogen-α ligand binding domain is thought to have potential in cancer therapy (see 1sj0-q1).

This query gave more hits than typical jobs with jobs taking longer than average.


L Zhao and R D Brinton, J Med Chem (2005) 48.10 3463-6

Extended Cancer Query - 1GI8-Q1

The Cancer Query 1GI8-Q1 Secondary Cancer, Urokinase plasminogen activator (uPA) has been extended into a wider range of molecules.

So it good news for the target :)

Arthritis - 1FDK-Q1 - Phospholipase A2 (PLA2)

Proteome
1FDK-Q1
Phospholipase A2 ( PLA2 )

Phospholipase A2 (PLA2) cleaves ester bond in glycerophospholipids releasing free fatty acids and lysophospholipids. Excessive levels of human nonpancreatic PLA2 has been associated with a number of disease states including arthritis, septic shock and atherosclerosis. Inhibition of PLA2 may have therapeutic potential in the treatment of arthritis. This query is based on a different crystal structure to 1fx9-q1.

Job times for this query are variable with some jobs taking less time than usual and giving very few hits.

J S Sawyer et al J Med Chem (2005) 48.3 p893-6

Cancer - 1Y6B-Q1 - Vascular Endothelial Growth Factor Receptor 2 (VEGFR2)

Cancer
1Y6B-Q1
Vascular Endothelial Growth Factor Receptor 2 ( VEGFR2 )

VEGF stimulates the growth of blood vessels. The uncontrolled growth of cancer cells is legendary. But this sort of growth requires a lot of blood flow to the cell area. If the blood vessel growth can be restrained, then, in theory, so can growth of the tumour. This query is based on a different crystal structure to 1y6a-q1.

The times for test jobs of this query were typical and gave average numbers of hits.


P A Harris et al J Med Chem (2005) 48 1610

Hepatitis C - 1DY8-Q1 - Hepatitis C Virus NS3 Serine Protease

Proteome
1DY8-Q1
Hepatitis C Virus NS3 Serine Protease

NS3 serine protease expressed by the hepatitis C virus is a recognised target for drug design. While some high molecular mass peptides have worked in the laboratory they are not suitable as drugs and the search for typical drug-like molecule has been less successful. This query is based on a different crystal structure to 1DY9-Q2.

The time taken by test jobs was variable usually giving fewer hits than average with most jobs completing relatively quickly.

S Di Marco et al J Biol Chem (2000) Vol 275, p7152

Alzheimer - 1UTT-Q1 - Macrophage Elastase

Proteome
1UTT-Q1
Metalloproteinase-12 ( MMP-12 )

Metalloproteinase-12 (Mmp-12) is also known as Macrophage Elastase and has been suggested as a possible drug target in the treatment of Alzheimer's disease. MMP-12 is also known to play a role in inflammatory processes including emphysema reducing lung function and also in Multiple Sclerosis where it may mediate the deposition of Amyloid proteins.

Job times for this query varied sometimes taking longer than typical jobs and giving above average numbers of hits.


R Morales et al J Mol Biol (2004) 341 p1063

Small stats glitch

THINK has just posted the following information and since most the un-official stats sites take their infomation from the CSV files they too will show the errors.

We had a problem on the inhouse stats server which truncated history3436.csv. This means that some jobs which were uploaded between 18:00 and 24:00 GMT yesterday will be included in the totals but not listed by jobs1.php. We will investigate correcting this next week.