The grid-treatment

This morning I've been sitting in the biomed session on the last day of ISGC2010. Among the talks was a presentation on research EUAsiaGrid is supporting into Dengue fever.

I spoke to Ying-Ta Wu, one of the brains behind the project, about this yesterday. As an associate research professor in the Genomics Research Centre in Academia Sinica, Wu's main responsibility is in drug screening. He is searching for a small molecule or compound that will interact and inhibit NS3, a protein which is important for Dengue virus proliferation.

Read on below to find out what he said (and also take a look at this great article on the subject in iSGTW this week).

GridCast: Why have you chosen to study Dengue fever?
Wu: Currently there's no drug available for Dengue fever apart from traditional medicines that are not based on scientific research. Dengue is not a top priority for pharmaceutical companies because it is regional and only occurs in developing and under developed countries which are not considered to be a big market.

GC: How would researchers usually find new drugs?
W: Usually in drug discovery, researchers would expression this protein and set up an assay protocol to measure the protein's activity. If a molecule interacts with this protein, it would reduce its activity.  That would all be done in the wet lab.

GC: What are the problems with this?
W: There are many many compounds available so it's very expensive and it's not a very good idea to test each individual compound one by one. So you need to have some strategy. In the Genomics Research Centre we have a big automatic screening system – a robotic system – which can screen a large amount of compounds a day. But even so, it's very costly and takes a lot of time to prepare and do the work.

GC: What approach are you taking?
W: In this anti Dengue virus project we're taking another strategy where we do virtual screening before the wet lab. Instead of doing the wet lab experiments, we are modelling the interaction of individual compounds with NS3 and from there then we measure and compute their interaction energy. We select compounds which have a very good interaction with the protein - we call it a 'potential hit.' We then analyse those potential compound structures to extract information about the structure. That information we submit to the chemist and they will synthesise a drug based on that information.

GC: What are your results so far?
W: We have already screened 300 000 compounds, and have got about 2000 potential hits. Those hits can be clustered based on their structure and similarity into 183 groups. Groups with large member sizes and with high average interaction energies are then suggested to the medicinal chemists.

We've already submitted that information to the biologists and chemists we're working with. Our collaborator Dr Doman Kim from Korea, uses this information for assays in the wet lab. He's started this but we haven't got the results yet.

GC: What tools are you using to carry out the virtual screening?
W: The tool we're using is called GVSS developed by EUAsiaGrid. On this platform the participants can submit their own library [of compounds to test]. If they don't have their own library we can prepare one for them. But we really encourage more people to join us and submit their own libraries or even other targets – all they need is the protein data bank information.

The beautiful thing about GVSS is that even people who don't know about computational methods can easily submit their job. For people doing the virtual screening, we have to screen a lot of compounds. It's very difficult to set up, because you have to prepare a lot of compounds you have to prepare the target and then most of all ,you have to find enough CPUs, enough resources.  Even if you do have enough CPUs you don't know how to submit the screening on a big scale. With GVSS all you do is click the target, decide the compound and just submit.

GC: What are the benefits of using this method?
W: I think the benefit is we can actually have more people in this area join the work against fighting a common disease. They can share their library, their data and their computer hours once they join EUAsiaGrid. We're currently collaborating with groups from Vietnam, the Philippines, Malaysia, Indonesia, Korea of course Taiwan!

If users are interested in any other disease or any other target they can submit their target to GVSS too, they just need the PDB file of the target. The exciting thing is we can have people gear up to fight those less interesting targets of pharmaceutical companies.

GC: So what's next?
W:I think the next step is to wait for the data and then we'll try to see what we can adjust the virtual screening model accordingly. We would like to get more and more people to know about this platform so we can form a power source to work towards the same target.