Project Information

User avatar
Alez
[ TSBT's Pirate ]
[ TSBT's Pirate ]
Posts: 10363
Joined: Thu Oct 04, 2012 1:22 pm
Location: roaming the planet

#1 Project Information

Post by Alez »

Main project page here

Right now we are developing methods for polyharmacological drugs development. Dual-targeting drugs.
As case study is taken goal to develop Tankyrase and PI3K inhibitors for treatment of colorectal cancer. This is relevant to other cancers as well. Especially are targeted those cancers, which have cancer stem cells actively involved and cancers on metastasis stage.

The currently dominating concept is "one target-one drug". Target means for example protein (in most cases), but can be DNA, RNA etc.
But most of the drugs are promiscuous, so even so called "one-target" drugs usually target something else also and usually this leads to side effects. Most of the approved drugs have side effects, but just less damaging than disease.
Polypharmacology concept suggests that making drugs, targeting more than one target (dual-targetin for example) will reduce side effects and may increase efficiency per quantity of the drug used.

So, polypharmacology:
1. Less side effects
2. More efficient
3. Cheaper
Currently we have selected two biotargets - Tankyrase (my postdoc expertise in one of the leading labs, in Norwegian Cancer cluster) and PI3K (its inhibition is synergistic to tankyrase).
So we are doing two things - developing new molecules and developing methods for polypharmacology.


We are doing this using three software programs for DrugDiscovery@home:
GROMACS - molecular dynamics
Autodock Vina - molecular docking
Autodock Smina - fork of Vina. It allows more customization and usage of our own (or just external) scoring functions. That is a very important change.

We are also using pharmacophore-based screening, QSAR and ADME/Tox filtering, but those are not computing power demanding for the amount of compounds, which we process now (starting database is around 3-4 mln compounds). After filtering we got database of 750 K compounds.

We have some preliminary agreements with MIPT (Moscow Institute of Physics and Technology) and Stanford University for testing the compounds, which we´ll find perspective.

The main scientific part now - is working on more or less universal consensus scoring function for Smina.

We also want to participate in D3R challenge (https://drugdesigndata.org/about/grand-challenge).
Unfortunately I´ve got information about this challenge only last week and not so much time left to participate.
However, we plan to participate in different kinds of international challenges.

So, on top of competition to crunch, there will be also competition in methods application toward tasks, participation in international competitions.
Image
The best form of help from above is a sniper on the rooftop....
User avatar
Alez
[ TSBT's Pirate ]
[ TSBT's Pirate ]
Posts: 10363
Joined: Thu Oct 04, 2012 1:22 pm
Location: roaming the planet

#2 Re: Project Information

Post by Alez »

for info Smina - a fork of Vina.
Smina does same tasks as Vina, just about 10 times faster.
At the moment only Linux 64bit version is available.

Smina application and source files are available here:
https://sourceforge.net/projects/smina/
Image
The best form of help from above is a sniper on the rooftop....
Post Reply Previous topicNext topic

Return to “DrugDiscovery”