FADVIEW - New Progress & Stats monitor

There a new Windows based Find-a-Drug monitoring program called FaDView by Gene_Galaxo from Bodensee-Team

It's still in it beta state, built using Delphi2005 but it's not open source like some of the other monitors.
Will monitor both Windows and Linux based but there's no current instruction of use, just left click and right click everywhere to find out what you can do.
It works well but only with the FaD client v1.30 beta's, you also need THINK_KDFOLD=Yes in your think.env file


FADView Screen shots

Cancer - 1YCQ-Q1 - Human Double Minute 2 (HDM2) bound to p53

Cancer
1YCQ-Q1
Human Double Minute 2 (HDM2) bound to p53

The p53 tumour suppressor protein regulates cell proliferation in cancer tumours. The binding of HDM2 to p53 has been observed to inhibit the action of p53 in one-third of soft tissue sarcomas. A small drug molecule which can binding to HDM2 would offer a novel cancer therpy with the potential to enable p53 to stop growth or kill the cancer cells.
This query is based on a different crystal structure to 1ycr-q3.

Test jobs for this query gave above average numbers of hits with longer job times.


P H Kussie et al Science (1996) 274 p921-2.

Proteome - 4PRG-Q1 - anti-diabetic, anti-obesity

Proteome
4PRG-Q1
Peroxisome proliferator-activated receptor g(PPAR-g)

The peroxisome proliferator-activated receptors g(PPAR-g) are ligand-activated transcription factors belonging to the nuclear receptor family. The therapeutic potential of this receptor is not fully appreciated. It has been suggested that this is a possible target for anti-obesity drugs and anti-diabetic - although some selectivity may be required.
This query is based on a different crystal structure to 1i7i-q1.

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


P Cronet et al Structure (2001) 9.8 p699-706

Cystic Fibrosis - 1R0X-Q1 - Respiratory

Respiratory Diseases
1R0X-Q1
Cystic fibrosis transmembrane conductance regulator (CFTR)

Cystic fibrosis transmembrane conductance regulator (CFTR) plays a role in cystic fibrosis. Its Nucleotide-binding domain 1 (NBD1) is often observed with at least one mutation although the biochemical significance of this is not fully understood. This is a speculative query to find molecules which might be therpeutically useful.

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


H A Lewis et al, EMBO J (2004) 23.2 p282-93

Multiple Sclerosis - 1PKQ-Q3 - Myelin Oligodendrocyte Glycoprotein

Well the 1PKQ-Q1 went fast so and I'm assuming this is a revised version of it..


Multiple Sclerosis
1PKQ-Q3
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 first 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.


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

Proteome - 1I7I-Q1 - anti-diabetic, anti-obesity

Proteome
1I7I-Q1
Peroxisome proliferator-activated receptor g(PPAR-g)

The peroxisome proliferator-activated receptors g(PPAR-g) are ligand-activated transcription factors belonging to the nuclear receptor family. The therapeutic potential of this receptor is not fully appreciated. It has been suggested that this is a possible target for anti-obesity drugs and anti-diabetic - although some selectivity may be required.

The test jobs took less time than typical jobs and with few hits.


P Cronet et al Structure (2001) 9.8 p699-706

Multiple Sclerosis - 1PKQ-Q1 - Myelin Oligodendrocyte Glycoprotein

Multiple Sclerosis
1PKQ-Q1
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 first 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.

Test jobs for this query gave relatively few hits and took less time than average jobs.


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

Cancer - 1T29-Q2 - Breast

Cancer
1T29-Q2
Breast Cancer Type 1 Susceptibility Protein (BRCA1)

Breast Cancer Type 1 Susceptibility Protein (BRCA1) is thought to play a role in breast and ovarian cancers. It is known that mutations play a role but it is not clear whether inhibiting BRCA1 will be therapeutically useful. This is query is based on a different crystal structure to 1t15-q1.

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



E N Shiozaki et al Mol Cell (2004) 14.3 p405-12.

Proteome - 1C8L-Q3 - antidiabetic

Proteome
1C8L-Q3
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 and 1b4d-q1.

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

Respiratory - 1SVC-Q1 - NF-k-b

Respiratory Disease
1SVC-Q1
NF-k-b

NF-k-b is a transcription factor. It has been suggested that it is a viable anti-inflammatory protein target which may be useful in treating respiratory diseases.

We expect this query to give fewer hits than normal in less time than typical jobs.-b is a transcription factor. It has been suggested that it is a viable anti-inflammatory protein target which may be useful in treating respiratory diseases.

We expect this query to give fewer hits than normal in less time than typical jobs.


C W Muller et al Nature (1995) 373 p311-7

Methodology - 1M17-Q3 - Prediction Improvement

Methodology
1M17-Q3
Epidermal growth factor receptor

Two-thirds of solid tumors arise from epithelial tissues, and studies suggest that EGFR inhibitors can stabilize or shrink many of these malignancies. It is conceivable that EGFR inhibitors could beneficial in therapies for cancers of the lung, pancreas, head and neck, breast, prostate, colon, stomach, ovaries, and brain. However, the initial inhibitors in clinicals trials where less successful than expected. In this project, we hope to find more effective molecules.

This query is a variation of 1m17-q2 which we hope will give more and better hits. Job times will be longer than 1m17-q2.


J Stamos, M X Sliwkowski and C Eigenbrot J Biol Chem (2002) Vol 277 p46265

1.30b beta released to testers

Beta tester upgrade time again v1.30b of the client is available to download.

Current details for 1.30b


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.
  - The configuration has to be saved (in the Find-a-Drug control panel) for existing installations.
  - When the software is already running, you must restart the PC to start the service.
  - A networked client running as service cannot open any windows - and the controls for doing so are not on the tray icon menu.
• 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 fadsetup.dat and is not backwards compatible with isetup.dat.
• 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.
• Under battery power with 1.30b, THINK goes to sleep (after a short delay) and FaDsetup will not attempt to wake it until mains power resumes. This contrasts with 1.30a when loader would not start the software and FaDsetup put THINK to sleep.
• 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.

Fixed problems

• Running networked clients as a service - 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.
• Jobs often failed when upgrading from 1.25 to 1.30 1.30b resolves this problem.
• Jobs complete immediately when continued after no hits - This problem was reporting under Linux and has been resolved in 1.30b.
• Query name and CPU time omitted from .tip files Under Linux with 1.30a the computer.tip files did not include the query name or CPU time. - This has been resolved under 1.30b.

Cancer - 1T15-Q1 - Breast

Cancer
1T15-Q1
Breast Cancer Type 1 Susceptibility Protein (BRCA1)

Breast Cancer Type 1 Susceptibility Protein (BRCA1) is thought to play a role in breast and ovarian cancers. It is known that mutations play a role but it is not clear whether inhibiting BRCA1 will be therapeutically useful.

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



E N Shiozaki et al Mol Cell (2004) 14.3 p405-12.

Malaria - 1LS5-Q2 - Plasmepsin IV

Malaria
1LS5-Q2
Plasmepsin IV

Plasmodium falciparum (the parasite which causes Malaria) invades erythrocyte cells and consumes the host hemoglobin. Plasmepsin plays a key role digesting the protein and has been recognised as a novel target for anti-malaria drugs. Inhibition of hemoglobin degradation lead to toxic concentrations and parasite death in culture. This query is based on a different crystal structures to 1lf2-q1 and 1lee-q1.

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



O A Asojo et al Acta Cryst (2002) d58 p2001

Methodology - 1DMW-Q1 - Phenylalanine hydroxylase

Methodology
1DMW-Q1
Phenylalanine hydroxylase

This is one of several metabolic proteins which may cause undesirable side-effects if a drug interaction occurs. Phenyalanine hydroxylase (PAH) deficiency results in intolerance to the dietary intake of the essential amino acid phenylalanine and produces a spectrum of disorders including phenylketonuria (PKU), non-PKU hyperphenylalaninemia (non-PKU HPA), and variant PKU. A side-effect or drug interaction could cause similar symptoms.

The jobs times are expected to be slightly shorter than typical giving above average numbers of hits.



H Erlandsen et al Biochemistry (2000) 39.9 p2208-17

New Query - Diabetes - 1B4D-Q1

Proteome
1B4D-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.

The test jobs took 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

1.30b beta early next week

Find-a-Drug client 1.30b should be out Monday (13/6) or Tuesday (14/6) if all goes well.

Fixes to include

• Upgrading from 1.25g causing failed jobs
• Allowing network clients to run without changing the default network access permissions

New Query - Respiratory - 1R55-Q1 - Asthma

Respiratory Disease
1R55-Q1
Adam33

Adam33 is a putative asthma susceptibility gene encoding for a membrane-anchored metalloprotease belonging to the ADAM family. The ADAMs (a disintegrin and metalloprotease) are a family of glycoproteins implicated in cell-cell interactions, cell fusion, and cell signaling. An inhibitor is sought as a potential treatment for Asthma.

We expect these jobs to give more than typical numbers of hits with with some longer than typical job times.



P Orth et al J Mol Biol (2004) 335.1 p129-37

New Query - Cancer - 1GS4-Q1

Cancer
1GS4-Q1
Androgen receptor (AR)

5-αdihydrotestosterone binds to the Androgen receptor (AR) and is believed to play a role in the development of at least some types of prostate cancer. Reducing the level of AR hinders cancer growth. This query is derived from a mutant AR which is associated with cancer.

This query gives above average numbers of hits with job times often longer than typical.


P M Matias et al J Med Chem (2002) 45 p1439

New Query - Proteome - 1W7H-Q1 - Inflammation

Proteome
1W7H-Q1
P38 MAP kinase

This protein plays a crucial role in regulating the production of proinflammatory signalling molecules of the immune system. Consequently, blocking the function of this kinase using a small molecule inhibitor has potential as an effective therapy for treating a wide range of inflammatory diseases. This query is based on a different crystal structure to 1kv2.

The job times vary but take about 10 hours on average on a typical PC giving more than typical numbers of hits.


C Pargellis et al, Nat. Struct. Biol. (2002) 9.4 p268-72

New Query - Cancer - 1C4Z-Q1

Cancer
1C4Z-Q1
E6AP ubiquitin-protein ligase

The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer. Inhibiting this interaction may be therapeutically useful preventing and treating cervical cancer.

Test jobs ran faster than average jobs giving few hits.


L Huang et al Science (1999) Nov 286 p1321-6



---

Science Magazine article
Structure of an E6AP-UbcH7 Complex: Insights into Ubiquitination by the E2-E3 Enzyme Cascade
Lan Huang, Elspeth Kinnucan, Guangli Wang, Sylvie Beaudenon, Peter M. Howley, Jon M. Huibregtse, and Nikola P. PavletichScience Nov 12 1999: 1321-1326.

1.30a BETA starts - problems

Well 1.30a BETA was released today, so all beta testers will get it on there next download or jump in now and hit recieve

--- Think
Members participating in the beta test will now be automatically upgraded to 1.30a. Initially, we are looking for issues which affect continued usage and then later we would like feedback on the added functionality.

You may experience problems if you attempt to downgrade to 1.25g including failure of current jobs. Do NOT downgrade unless you believe this is essential.
---

Problems already found
After updating to 1.30a the current job seems to be failing instantly, so you may want to hold of that update till you fininsh a job.

FaD Servers Changed

Posted by Think
---
find-a-drug.org.uk and find-a-drug.org have now moved server. The midnight stats run will update the new server whereas the 18:00 GMT stats run updated the old server! www.find-a-drug.com and the stats servers were updated normally.

Some posts to the forum may have been lost.

We had no notice of this change although we were aware that it would happen sometime. At this time, we have no reason to believe that any jobs have been lost but some have been delayed by over 24 hours.
---

So if you see a problem, wait a day to report it ;-)

New Query - Respiratory - 1IRJ-Q2

Respiratory Disease
1IRJ-Q2
MRP14

MRP14 is a Ca(2+)-binding protein from the S100 family of proteins thought to play a role during inflammation of membranes.

We expect this query to give above average numbers of hits with longer job times than typical.



H Itou et al, J Mol Biol (2002) 316.2 p265-76.

New Query - Proteome - 1HZJ-Q1

Proteome
1HZJ-Q1
UDP-galactose 4-epimerase

UDP-galactose 4-epimerase catalyzes the interconversion of UDP-galactose and UDP-glucose during normal galactose metabolism. An inhibitor would be expected to have anti-bacterial properties although if the molecule was non-selective there would be a risk of galactosemia as a side-effect.

Job times for this query varied with an average time less than 10 hours on a typical PC and above average numbers of hits.



J B Thoden et al, J Biol Chem (2001) 276.18 p15131-6