1.30a beta client soon

The 1.30a beta client should be going into beta testing by the end of next week (eta morning 3rd May)

If you do NOT wish to participate in this beta test please ensure that you have opted out in the Find-a-Drug control panel prior to 10:00 GMT Tuesday

changlog

Loader

• A local copy is now used on networked nodes under Windows which starts the central copy once this node is accessible (or times out after 15 minutes).

Setup

• The software can now run as a service. New installations of the software are configured as a service (XP,200x) or a scheduled task (ME,98) by default.
  
• A scheduling option allows the software to run only at specified times during weekdays or weekends. This could be used to avoid running the software during working hours.
  
• It is now possible to use proxy settings under Windows separately from Internet Explorer.
  
• The configuration data stored in isetup.dat has been revised and is not backwards compatible.
  
• We believe we have fixed a problem which could lead to the configuration data being corrupted.
  
• When saving the configuration, the software now retries with alternative servers listed in cgi.lis before reporting a failure.
  
• The status bar now reports the same information as the tool tip.
  

THINK client

• In mixed Linux/Windows installations, THINK no longer writes directly to the queue. Instead data is written to a temporary file which server then reads and writes to the queue. This should avoid some obscure queue errors.
  
• Under certain circumstances such as a system failure, the results file and the progress file could be out of synchronisation. When THINK restarts it now checks that the files are compatible and if not restarts from after the last recorded hit. This should reduce or eliminate jobs being rejected because the results file is missing data.
  
• Some internal and algorithmic changes have also been made.

Job queue server

• The output from "Client Info" has been extended to include the CPU rating and CPU time (this requires KDFOLD=YES to be present in think.env). This uses data from files named computer.tip which replace pcname.nnn previously written.
  
• Under Linux, "file not found" messages no longer occur during initial startup of the software.
  

Automatic Upgrade

• This upgrade should proceed automatically and take about 2 minutes.
  

Outstanding problems

• fadsetup.scr can crash THINK Under Windows XP when FaDsetup is configured as the screensaver, it often causes THINK to crash when it starts.
  
• Linux messages Under Linux there are no messages written to the screen during an upgrade (although there are to server.log and loader.log). This can cause confusion.

New Query - Cancer - 1NKP-Q3

Cancer
1NKP-Q3
MYC-MAX transcription factor

MYC-MAX transcription factor determines whether a cell will divide and proliferate. Deregulation of MYC has been implicated in the development of many human cancers, including Burkitt's lymphoma, neuroblastomas, and small cell lung cancers. An effective transcription inhibitor may have therapeutic potential in cancer. This query is a revision of 1nkp-q2.

In test jobs, the time taken was typical with fewer hits than usual but more than 1nkp-q2.


S K Nair and S K Burley Cell (2003) 112.2 p193-205
Download the Full PDF Full HTML

New Proteome Target - 1PTZ-Q1

Proteome
1PTZ-Q1
Superoxide dismutase

Mutations in Superoxide dismutase (SOD) have been associated with Lou Gehrig's disease (also known as ALS) which is the most common form of motor neuron disease. When neurons in the spinal cord die this leads to muscle wasting and total paralysis. For an inhibitor to have any therpeutic value it would need to selectively inhibit mutant SOD.

The time taken by test jobs varied greatly often taking longer than typical jobs giving above average numbers of hits.


D DiDonato et al J Mol Biol (2003) 334.1 p175

Multiple Sclerosis feedback ?

The Question was asked (hob)
"Any News Yet"

The answer was (Think)
"Yes we've been in contact (although they're busy)
Yes they've made interesting progress (but I can't disclose unpublished details even if I had them)
Yes I have reason to expect some more MS queries in the coming months."

So looks like we have been useful.
Look's like we get the chance to be useful again.

New Query - Respiratory Diseases - 1JQE-Q1

Respiratory Diseases
1JQE-Q1
Histamine methyl transferase

The hormone histamine plays a key role in bronchial asthma as well as gastric acid secretion. Histamine interacts with histamine methyltransferase. Molecules which block this interact have capability to be new anti-histamine drugs for asthma treatment. This query is based on a different crystal structure than 1jqd-q2.

We expect this queries to give normal numbers of hits with in typical times.


J R Horton et al Structure (2001) 9.9 p837-49

Extended Query - Cancer - 1UU3-Q1

1UU3-Q1 Phosphoinositide dependent protein kinase (PDK1) has been extended (which is always a good sign)

Looking at the initial set they are long jobs averaging around 16hrs
http://www.find-a-drug.org.uk/1uu3-q1r.htm

New Query - Methodology - 1EL3-Q2

Methodology
1EL3-Q2
Aldose Reductase

In general, a drug which in addition to its intended action interferes with the normal metabolic processing or signalling is likely to exhibit side-effects. It has also been suggested that Aldose Reductase can mediates certain diabetic complications such as hyperglycemia; metabolises toxic aldehydes; and stimulates an inflammation response.

In test jobs, this query gave more hits than usual taking less time than typical jobs.


V Calderone et al, Acta Cryst D (2000) 56 p536-40

New Queries - Proteome & Cancer

Proteome
1DVY-Q3
Transthyretin

The human amyloid disorders (including polyneuropathy, cardiomyopathy and senile amyloidosis) are caused by insoluble transthyretin (TTR) fibrils being deposited in the peripheral nerves and heart tissue. It has been suggested that inhibiting TTR may have therapeutic value by stopping the formation of such fibrils.

Test jobs gave below average numbers of hits in less time than typical.


T Klabunde et al Nat Struct Biol (2000) 7.4 p312-21.






__________________



Cancer
1SJ0-Q1
Estrogen 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


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

Interesting article
Suggestions it may also valuable for lung cancer as well as cancers of the breast, uterus and ovaries

Stats server 'uneventful' problem

The in-house stats server had a problem but was fixed, did anyone notice...
not me...

P.S. No jobs have been lost so you can breath easily :D

New Query - Cancer - 1S9J-Q1

This is the MEK1 version of 1S9I-Q1 (which was MEK2)

Cancer
1S9J-Q1
Mitogen-Activated Protein Kinase 1 (MEK1)

Mitogen-Activated Protein Kinase 1 (MEK1) is a tyrosine/threonine protein kinases found in the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway. This growth pathway is activated in many cancers and inhibiting it might be a useful cancer therapy for certain tumours.

In test jobs the time taken varied but was often longer than 1S9I-Q1 (MEK1) giving at least typical numbers of hits.


J F Ohren et al Nat Struct Mol Biol (2004) 11.12 p1192-7

20 old queries closing

20 of the older queries will be closed to results on the 10th May 2005

These will be

1b7y-q2
1vkg-q1
1rwx-q1
1lru-q1
1mp1-q1
1xa5-q2
1bo9-q2
1ycs-q1
1t67-q2
1p4f-q1
1d5c-q1
1k4t-q3
1hsh-q1
1nx3-q1
1qiw-q1
1s2a-q1
1bv9-q1
1cr6-q1
1fkn-q3
1r6n-q3

New Query - Cancer - 1S9I-Q1

Cancer
1S9I-Q1
Mitogen-Activated Protein Kinase 2 (MEK2)

Mitogen-Activated Protein Kinase 2 (MEK2) is a tyrosine/threonine protein kinases found in the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway. This growth pathway is activated in many cancers and inhibiting it might be a useful cancer therapy for certain tumours.

In test jobs the time taken varied but was often less than typical jobs giving at least typical numbers of hits.


J F Ohren et al Nat Struct Mol Biol (2004) 11.12 p1192-7

New Query - Malaria - 1D6N-Q1

Malaria
1D6N-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.

In test jobs, this query gave more hits than usual taking more time than typical jobs.


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

New Query - Proteome - 1UKH-Q1

Proteome
1UKH-Q1
c-Jun N-terminal kinases (JNKs)

c-Jun N-terminal kinases (JNKs) is a mitogen-activated protein kinase (MAPK) and they are thought to play a role in cell death (JNK3), immune cell function (JNK1 and JNK2), and progressive neurological disease (JNK1). We have previously targeted JNK1 (1PMN-Q1) and selectivity for JNK3 over JNK1 may be important therapeutically.

Test jobs gave above average numbers of hits taking longer than typical.


L Resnick & M Fennell DDT (2004) 9.21 p932-939

New Cancer Target - 1LUJ-Q1

Cancer
1LUJ-Q1
ß-Catenin

ß-Catenin is a multifunctional protein involved in both cell adhesion and transcriptional activation. It has been suggested that for some cancers inhibiting ß-Catenin has therapeutic potential.

The time taken and numbers of hits varied significantly in test jobs


T A Graham et al Mol Cell (2002) 10.3 p563-71

An opportunity for some FaD members to contribute more ..

This is slightly old news but the offer is still there.
http://www.find-a-drug.org.uk/forums/viewtopic.php?t=4753
(stickied in the projects section)

THINK (Keith Davis) asked back at the end of February if some skilled members would like to help out with a different aspect to crunching.

From time to time, we have been fortunate to have members volunteer to assist with running this project in various ways including moderating this forum, suggesting protein targets, developing code for some of the stats, certificates and programming. This year we are looking for more help to identify academic research groups who are interested in finding inhibitors for proteins with known 3D structures. It is proposed to use robotic engines to search for websites that reference proteins by name and certain keywords indicative of this research work.

The project is being divided into the following tasks:
0. Design and implement a database (in MySQL) to store the relevant information.
1. Extract protein names from PDB files.
2. Associate proteins with disease conditions and projects.
3. Locate and rank websites for academic groups of interest using robotic search engines. It is envisaged that a student from Sheffield University will assist in this phase.
4. Build (in PHP) a web based front-end to search and review the data
5. Review the websites identified to confirm a valid interest in a protein target.

Any-one interested in assisting should e-mail Keith.Davies@find-a-drug.org.uk with an outline of their skills and relevant experience. Thank you.
PS I'm the guy in charge of Find-a-Drug (This means I take all the blame and give all the credit to others)

New Targets

2 new targets available


Cancer
1NKP-Q2
MYC-MAX transcription factor

MYC-MAX transcription factor determines whether a cell will divide and proliferate. Deregulation of MYC has been implicated in the development of many human cancers, including Burkitt's lymphoma, neuroblastomas, and small cell lung cancers. An effective transcription inhibitor may have therapeutic potential in cancer.

In test jobs, the time taken was typical with fewer hits than usual.


G S Sheppard et al Bioorg Med Chem Lett (2004) 14.4 p865-8




------------------------------------------

Respiratory Diseases
1BKC-Q1
TNF-alpha


The name Tumor necrosis factor-a (TNF-alpha) originates from its ability to kill tumor cells. It is a cytokine that induces protective inflammatory reactions but also causes severe damage when produced in excess, as in rheumatoid arthritis and septic shock. Our interest is in respiratory disease where it is also a recognised potential drug target. In test jobs, this query gave more hits than usual in typical times.


K Maskos et al Proc Natl Acad Sci (1998) 95.7 p3408-12

Forum planned maintenance

Find-a-Drug :: View topic - Forum planned maintenance

Changes are being made in an attempt to prevent further Guest based Denial of Service (DoS) attacks.

Thereafter it will be necessary to visit the forum using links on the main websites or via the URL http://www.find-a-drug.org/forums.html It will NOT be possible to access the forum using the URL http://www.find-a-drug.org.uk/forums Direct links from other forums and websites to forum topics, posts etc will no longer work. Links within the forum will work.

Guests will have read access to the forum but their session time will be limited to 1 hour.
....
You may also visit the forum using the URL http://www.find-a-drug.org/forums/forums.php

Any problems please post or e-mail support@find-a-drug.org.uk

Client beta 1.3x

The next beta testing of a new client should begin near the end of April.

• Improvement to a 'service' setting for WinXP/2K/2K3 and scheduled task setting for Win9x/ME are in the pipeline.
• Fast and Slow job delegation to appropriatly power computers
• Notification Icon improvements (i.e. fixed the annoying system tray icon dissapearing)
• Better connection options (scheduling times, proxy ?)
• Scientific/algorithmic enhancements

Of course this could change and it's likely to slip into early May

Start of the FaD blog

Well I thought I would create somewhere I could pass on Find-a-Drug information and news, it may just include some wibble from time to time.