Projects - HIV

Protein

Description

Statistics

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.



 
query: 1C70-Q1
% jobs complete: 100.000
molecules: 510,447,593
hits: 4,283,499
time: 187:226:06:48:08
Pictures   P J Ala et al Biochemistry (1998) 37.43 p15042-9   last updated: 12:00 on 26-JAN-06

HIV Integrase

 

HIV Integrase is considered a difficult target to inhibit. Merck have announced some success and this is the first of several Integrase queries which attempt to find novel inhibitors. The additional queries will target alternative binding sites. This query is based on a different crystal structure to 1hyv.

We expect this queries to give average numbers of hits with below average job times.



 
query: 1BIS-Q1
% jobs complete: 0.000
molecules: 0
hits: 0
time: 0:000:00:00:00
Pictures   Y Goldgur et al, Proc Natl Acad Sci (1998) 95 p9150   last updated:

HIV Integrase

 

HIV Integrase is considered a difficult target to inhibit. Merck have announced some success and this is the first of several Integrase queries which attempt to find novel inhibitors. The additional queries will target alternative binding sites.

This query is a slight variation of 1hyv-q4.



 
query: 1HYV-Q4
% jobs complete: 79.770
molecules: 31,612,637
hits: 1,767,349
time: 12:275:13:19:24
Pictures   Y Molteni et al, Acta Cryst (2001) D57 p536   last updated: 18:09 on 01-APR-05

HIV-1 Protease

 

Protease inhibition is established as a key therapeutic approach limiting the progress of HIV. However, mutations of the virus protein have the consequence that resistance develops. This is one of a series of possible queries for HIV-1 protease which explore possible modes of inhibition with the view to finding novel inhibitors which are less susceptible to protein mutations.

We expect this queries to give above average numbers of hits. It requires features which have been added to THINK in version 1.23 and consequently the query will initially only be available to members participating in the beta test.



 
query: 1A30-Q1
% jobs complete: 100.000
molecules: 78,675,671
hits: 3,462,360
time: 112:124:23:51:28
Pictures   J M Louis et al, Biochem (1998) 37 p2105   last updated: 12:11 on 24-AUG-04

HIV-1 Protease

 

Protease inhibition is established as a key therapeutic approach limiting the progress of HIV. However, mutations of the virus protein have the consequence that resistance develops. This is one of a series of possible queries for HIV-1 protease which explore possible modes of inhibition with the view to finding novel inhibitors which are less susceptible to protein mutations.

This query has been derived from 1a30-q1 using some initial experimental results indicating activity. It is expected to give fewer hits and shorter jobs than 1a30-q1.



 
query: 1A30-Q2
% jobs complete: 100.000
molecules: 510,650,823
hits: 11,197,086
time: 289:242:23:04:34
Pictures   J M Louis et al, Biochem (1998) 37 p2105   last updated: 00:13 on 13-DEC-04

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.



 
query: 1A8G-Q1
% jobs complete: 100.000
molecules: 39,650,346
hits: 1,261,983
time: 31:225:18:28:25
Pictures   A B Smith III, J Med Chem (2003) 46.10 p1831-44   last updated: 00:00 on 26-JAN-06

Nef protein

 

Human immunodeficiency virus (HIV) Nef protein accelerates virulent progression of acquired immunodeficiency syndrome (AIDS) by its interaction with specific cellular proteins involved in signal transduction and host cell activation. Inhibiting Nef from binding to the Src family of kinases has therapeutic potential.

The time taken by our test jobs was variable but less than typical jobs.



 
query: 1AVZ-Q1
% jobs complete: 100.000
molecules: 39,627,768
hits: 11,124
time: 2:115:17:40:33
Pictures   S Arold et al, Structure (1997) 5.10 p1361-72   last updated: 06:08 on 29-MAR-05

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.



 
query: 1B6L-Q1
% jobs complete: 100.000
molecules: 39,651,646
hits: 612,352
time: 13:332:08:04:51
Pictures   A B Smith III, J Med Chem (2003) 46.10 p1831-44   last updated: 12:00 on 12-JAN-06

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 below average job times on a typical PC.



 
query: 1BDQ-Q1
% jobs complete: 100.000
molecules: 39,647,842
hits: 87,952
time: 2:319:03:26:45
Pictures   A B Smith III, J Med Chem (2003) 46.10 p1831-44   last updated: 18:00 on 20-JAN-06

HIV Integrase

 

HIV Integrase is considered a difficult target to inhibit. Merck have announced some success and this is the first of several Integrase queries which attempt to find novel inhibitors. The additional queries will target alternative binding sites. This query is based on a different crystal structure to 1hyv and replaces 1bis-q1.

We expect this queries to give average numbers of hits with below average job times.



 
query: 1BIS-Q2
% jobs complete: 100.000
molecules: 39,627,590
hits: 56,492
time: 1:136:03:45:29
Pictures   Y Goldgur et al, Proc Natl Acad Sci (1998) 95 p9150   last updated: 00:13 on 15-JUN-05

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.



 
query: 1BIU-Q1
% jobs complete: 100.000
molecules: 39,639,534
hits: 15,291
time: 10:189:00:27:10
Pictures   Y Goldgur et al, Proc Natl Acad Sci (1998) 95 p9150   last updated: 12:07 on 23-SEP-05

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 longer than average job times on a typical PC.



 
query: 1BV9-Q1
% jobs complete: 100.000
molecules: 39,627,671
hits: 559,851
time: 20:167:15:39:37
Pictures   P J Ala et al Biochemistry (1998) 37.43 p15042-9   last updated: 18:21 on 20-JUN-05

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.



 
query: 1C6X-Q1
% jobs complete: 100.000
molecules: 39,653,911
hits: 876,474
time: 33:120:07:09:45
Pictures   S Munshi et al Acta Cryst (2000) 56D p381   last updated: 18:00 on 20-JAN-06

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 average job times on a typical PC.



 
query: 1C6Y-Q1
% jobs complete: 100.000
molecules: 39,649,009
hits: 530,242
time: 30:043:20:08:22
Pictures   S Munshi et al Acta Cryst (2000) 56D p381   last updated: 12:00 on 20-JAN-06

HIV gp41

 

The entry of HIV into cells requires an interaction between proteins on the surface of the virus and human proteins (CD4 and a chemokine receptor) on the cell surface. It is understood that gp41 binding occurs after gp120 and that a peptide-like molecule which can bind to gp41 prevents HIV entering the cell. Peptide-like molecules have properties which make them unsuitable to be oral drugs. Finding a small molecule which can bind effectively to the gp41 helix will be quite challenging and we expect a low hit rate with this query. Any molecule we predict to be effective will need to be made and tested in the laboratory prior to clinical trials. This process usually takes many years.



 
query: 1CZQ-Q1
% jobs complete: 100.000
molecules: 39,877,795
hits: 0
time: 2:109:08:40:18
Pictures   D M Eckert et al Cell (1999) Vol 99 p103   last updated: 06:27 on 01-OCT-03

HIV gp41

 

The entry of HIV into cells requires an interaction between proteins on the surface of the virus and human proteins (CD4 and a chemokine receptor) on the cell surface. It is understood that gp41 binding occurs after gp120 and that a peptide-like molecule which can bind to gp41 prevents HIV entering the cell. Peptide-like molecules have properties which make them unsuitable to be oral drugs.

This query will only run under THINK 1.25b (or later revisions) and has some subtle but important improvements to 1czq-q1 which result in a moderate hit rate. Jobs usually take a few hours on a typical PC.



 
query: 1CZQ-Q2
% jobs complete: 100.000
molecules: 39,627,626
hits: 155,918
time: 15:021:14:09:46
Pictures   D M Eckert et al Cell (1999) Vol 99 p103   last updated: 00:12 on 04-MAR-05

Deoxyhypusine Synthase

 

Inhibiting this enzyme suppresses hypusine formation and the activation of a cofactor in the HIV-1 Rev regulatory protein. This inhibits the replication of the virus. It has been suggested that this is an attractive drug target because few side-effects are anticipated and especially useful for strains of HIV resistant to other drugs.

The time taken by our test jobs was variable with some jobs taking longer than typical jobs.



 
query: 1DHS-Q1
% jobs complete: 100.000
molecules: 39,627,397
hits: 217,036
time: 10:082:20:17:49
Pictures   D I Liao et al, Structure (1998) 6 p23   last updated: 12:09 on 03-APR-05

HIV gp120

 

The entry of HIV into cells requires an interaction between gp120 on the surface of the virus and human proteins (CD4 and a chemokine receptor) on the cell surface. We aim to find a small molecule which binds to the gp120 protein blocking the site where it would interact with CD4. This would effectively inhibit HIV entering the cell. We hope that because this site is largely conserved across the strains of HIV-1 that any inhibitor would be unaffected by mutations of the HIV virus. Any molecule we predict to be effective will need to be made and tested in the laboratory prior to clinical trials. This process usually takes many years.



 
query: 1G9M-Q3
% jobs complete: 100.000
molecules: 78,715,708
hits: 539,483
time: 85:249:16:00:11
Pictures   P D Kwong et al (1998) Nature 393 p648-659   last updated: 06:05 on 05-MAY-04

HIV gp120

 

The entry of HIV into cells requires an interaction between gp120 on the surface of the virus and human proteins (CD4 and a chemokine receptor) on the cell surface. We aim to find a small molecule which binds to the gp120 protein blocking the site where it would interact with CD4. This would effectively inhibit HIV entering the cell. We hope that because this site is largely conserved across the strains of HIV-1 that any inhibitor would be unaffected by mutations of the HIV virus. Any molecule we predict to be effective will need to be made and tested in the laboratory prior to clinical trials. This process usually takes many years.

This query is a revision of the earlier gp120 protein query 1g9m-q3. The job times are longer than typical jobs.



 
query: 1G9M-Q4
% jobs complete: 100.000
molecules: 39,627,328
hits: 233,563
time: 55:125:18:41:10
Pictures   P D Kwong et al (1998) Nature 393 p648-659   last updated: 18:14 on 10-APR-05

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 normal numbers of hits in average times on a typical PC.



 
query: 1HSH-Q1
% jobs complete: 100.000
molecules: 39,627,467
hits: 203,795
time: 5:154:00:30:09
Pictures   Z Chen et al J Biol Chem (1994) 269 p26344   last updated: 18:11 on 01-JUL-05

HIV Integrase

 

HIV Integrase is considered a difficult target to inhibit. Merck have announced some success and this is the first of several Integrase queries which attempt to find novel inhibitors. The additional queries will target alternative binding sites.

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



 
query: 1HYV-Q3
% jobs complete: 100.000
molecules: 510,526,007
hits: 46,727,075
time: 632:343:12:10:12
Pictures   Y Molteni et al, Acta Cryst (2001) D57 p536   last updated: 00:06 on 06-FEB-05

HIV Integrase

 

HIV Integrase is considered a difficult target to inhibit. Merck have announced some success and this is the first of several Integrase queries which attempt to find novel inhibitors. The additional queries will target alternative binding sites.

This query is still based on the 1hyv crystal structure. Most jobs complete in less than 1 hour.



 
query: 1HYV-Q5
% jobs complete: 100.000
molecules: 510,424,126
hits: 987,252
time: 15:231:21:59:06
Pictures   Y Molteni et al, Acta Cryst (2001) D57 p536   last updated: 00:06 on 22-SEP-05

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.



 
query: 1NPV-Q1
% jobs complete: 100.000
molecules: 39,650,119
hits: 230,283
time: 10:316:04:43:50
Pictures   P J Ala et al Biochemistry (1998) 37.43 p15042-9   last updated: 12:07 on 22-SEP-05

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.



 
query: 1NPW-Q3
% jobs complete: 100.000
molecules: 39,639,857
hits: 186,687
time: 18:046:12:04:38
Pictures   A B Smith III, J Med Chem (2003) 46.10 p1831-44   last updated: 06:04 on 01-NOV-05

HIV Integrase

 

HIV Integrase is considered a difficult target to inhibit. Merck have announced some success and this is the first of several Integrase queries which attempt to find novel inhibitors. The additional queries will target alternative binding sites. This query is based on a different crystal structure to 1hyv and 1bis.

We expect this queries to give above average numbers of hits with typical job times.



 
query: 1QS4-Q1
% jobs complete: 100.000
molecules: 39,627,372
hits: 0
time: 0:297:03:48:29
Pictures   Y Goldgur et al, Proc Natl Acad Sci (1999) 96 p13040   last updated: 12:11 on 27-JUN-05

HIV Integrase

 

HIV Integrase is considered a difficult target to inhibit. Merck have announced some success and this is the first of several Integrase queries which attempt to find novel inhibitors. The additional queries will target alternative binding sites. This query is based on a different crystal structure to 1hyv and 1bis. It is a variant of 1qs4-q1 which gives more hits!

We expect this queries to give above average numbers of hits with typical job times.



 
query: 1QS4-Q2
% jobs complete: 100.000
molecules: 39,627,579
hits: 102,813
time: 8:002:17:05:07
Pictures   Y Goldgur et al, Proc Natl Acad Sci (1999) 96 p13040   last updated: 18:09 on 16-JUL-05

Deoxyhypusine Synthase

 

Inhibiting this enzyme suppresses hypusine formation and the activation of a cofactor in the HIV-1 Rev regulatory protein. This inhibits the replication of the virus. It has been suggested that this is an attractive drug target because few side-effects are anticipated and especially useful for strains of HIV resistant to other drugs. This query is based a different protein crystal structure to 1dhs-q1.

The time taken by our test jobs was variable with some jobs taking longer than typical jobs but mostly giving fewer hits.



 
query: 1RQL-Q1
% jobs complete: 100.000
molecules: 39,652,767
hits: 44,903
time: 16:272:22:55:52
Pictures   D I Liao et al, Structure (1998) 6 p23   last updated: 18:00 on 25-JAN-06

HIV gp120

 

The entry of HIV into cells requires an interaction between gp120 on the surface of the virus and human proteins (CD4 and a chemokine receptor) on the cell surface. We aim to find a small molecule which binds to the gp120 protein blocking the site where it would interact with CD4. This would effectively inhibit HIV entering the cell.

This query is based on a different crystal structure to 1g9m. Job times and hits rates are expected to be typical.



 
query: 1RZJ-Q1
% jobs complete: 100.000
molecules: 510,425,239
hits: 3,234,660
time: 76:083:12:00:20
Pictures   C C Huang et al Proc Natl Acad Sci (2004) 101 p2706   last updated: 12:31 on 06-AUG-05

Rab9 GTPase

 

It has been suggested that Rab9 GTPase is a key cellular component for a variety of virus related diseases by facilitating vesicular transport. Our main interest in their target is as a HIV-1 drug target. This query is based on a different crystal structure of the same protein as the 1WMS-Q1 query.

We expect this query to give average numbers of hits with job times less than 12 hours on a typical PC.



 
query: 1S8F-Q1
% jobs complete: 100.000
molecules: 39,627,358
hits: 141,360
time: 2:258:00:10:21
Pictures   J G Wittmann and M G Rudolph, FEBS Lett (2004) 568 p23   last updated: 19:02 on 07-APR-05

Rab9 GTPase

 

It has been suggested that Rab9 GTPase is a key cellular component for a variety of virus related diseases by facilitating vesicular transport. Our main interest in their target is as a HIV-1 drug target.

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



 
query: 1WMS-Q1
% jobs complete: 100.000
molecules: 510,384,699
hits: 10,588,995
time: 153:064:05:12:11
Pictures   L Chen et al, J Biol Chem (2003) 279 p 40204-8   last updated: 00:08 on 02-AUG-05

Rab9 GTPase

 

It has been suggested that Rab9 GTPase is a key cellular component for a variety of virus related diseases by facilitating vesicular transport. Our main interest in their target is as a HIV-1 drug target. This query is based on a different crystal structure of the same protein as the 1WMS-Q1 and 1S8F-Q1 queries.

We expect this query to give above average numbers of hits with job times less than 12 hours on a typical PC.



 
query: 1YZL-Q1
% jobs complete: 100.000
molecules: 39,655,017
hits: 784,055
time: 16:007:19:13:30
Pictures   J G Wittmann and M G Rudolph, FEBS Lett (2004) 568 p23   last updated: 18:01 on 13-JAN-06