| Index | Recent Threads | Unanswered Threads | Who's Active | Guidelines | Search |
 |
World Community Grid Forums
Category: Completed Research
Forum: Discovering Dengue Drugs - Together
Thread: General questions regarding the drug discovery procedure |
| No member browsing this thread |
|
Thread Status: Active Total posts in this thread: 6
|
|
| Author |
|
|
Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
Hi all,
----------------------------------------being a layperson in the fields of biochemistry and pharmacology, I wondered about a few general things regarding the procedures and methods applied with drug discovery using Autodock and similar tools / techniques (more specifically in the case of the DDDT project), and hope that someone can shed some light on these: 1. How promising is this approach at all? IOW, is it guaranteed that prospective protease inhibitors will be found at all during phase 1? And if not: How high are the probabilities for a success? 2. Same for phase 2: Provided that enough potential ligands have been identified during phase 1, how are chances that effective inhibitors of flavivirus proteases will be found at all? IOW: Is this just a matter of mere number crunching effort which will eventually lead to a result - or can there just as well be a point at which all possible combinations have been computed, without any usable outcome? 3. How about the timeframe? Assuming that phase 2 has been successfully completed, how long does it typically take until drugs will be effectively available for therapy? Thank you in advance for any insight on the matter! [Edit 1 times, last edit by Former Member at Mar 25, 2008 10:52:31 PM] |
||
|
|
Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
There are no firm answers - there are no guarantees that a suitable inhibitor can be found. But, if there is a suitable drug out there waiting to be found, this approach is a good way of identifying it.
The FightAIDS@Home project (also using AutoDock) included known HIV protease inhibitors in their early experiments. The AutoDock software scored them highly. This means that if a suitable drug-like compound exists in the tested libraries, then AutoDock is highly likely to find it. One caveat: AutoDock's docking requires pre-knowledge of the mechanism used by the inhibitor. If the protease molecule has other active sites, then they may be overlooked - they will require separate docking attempts. Expect the timeframe to be long. The lead to drug time is typically years, and testing will take a long time, too. Remember, even negative results can be helpful. If scientists can do docking in-silico, they can devote more lab time to other approaches. |
||
|
|
Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
...and read the paper:
Analysis of HIV Wild-Type and Mutant Structur... Diverse Ligand Libraries Max W. Chang, William Lindstrom, Arthur J. Olson, and Richard K. Belew J. Chem. Inf. Model.; 2007; 47(3) pp 1258 - 1262; (Article) DOI: 10.1021/ci700044s |
||
|
|
Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
Thank you for your clarifications, Didactylos.
---------------------------------------- There are no firm answers - there are no guarantees that a suitable inhibitor can be found. But, if there is a suitable drug out there waiting to be found, this approach is a good way of identifying it. Okay, this is what I would have intuitively assumed, too. But I'm still wondering if the probability of the "suitable drug out there waiting to be found" existing can be quantified, based on former experience with similar approaches? Remember, even negative results can be helpful. If scientists can do docking in-silico, they can devote more lab time to other approaches. Makes a lot of sense. Thanks again for your input, and also for the link to the paper - I'm reading it right now. [Edit 1 times, last edit by Former Member at Mar 25, 2008 11:51:37 PM] |
||
|
|
retsof
Former Community Advisor USA Joined: Jul 31, 2005 Post Count: 6824 Status: Offline Project Badges: 
|
Remember, this is the drug PRESCREENING phase. We give the scientists some promising choices to test in the lab, rather then having them test them all. It should cut some time from the end.
----------------------------------------
SUPPORT ADVISOR
Work+GPU i7 8700 12threads School i7 4770 8threads Default+GPU Ryzen 7 3700X 16threads Ryzen 7 3800X 16 threads Ryzen 9 3900X 24threads Home i7 3540M 4threads50% |
||
|
|
DmitrIO
Cruncher Joined: Sep 21, 2007 Post Count: 11 Status: Offline |
2gstercken
Recently I've found an article connected with computational biology and chemistry. It's not about HIV and cancer, but it shows that results may, can and was found using computational methods. Here is an english version http://wis-wander.weizmann.ac.il/site/en/weizman.asp?pi=371&doc_id=5093 And for russian-speaking users http://lenta.ru/news/2008/03/24/enzyme/ |
||
|
|
|