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OpenSourceMalaria / OSM_To_Do_List

Action Items in the Open Source Malaria Consortium
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Collection of Previous Work Towards Series 4 Pharmacophore Model --> ELN #287

Open mattodd opened 9 years ago

mattodd commented 9 years ago

There's strong data suggesting OSM Series 4 hits PfATP4 as its Mechanism of Action. I posted an intro on this today

http://malaria.ourexperiment.org/the_osm_blog/11547/The_Mysterious_World_of_ATP4_Inhibitors.html

We will need a pharmacophore model for Series 4, to be predictive in drug design. This is a significant cheminformatics project. It's also pretty fascinating - take a look at the diversity of structures in the post above.

@murrayfold the first thing we need is for all your preliminary work on this from last year (which was not shared because Kiaran's paper was under embargo) to be shared on the ELN with a little context, here:

http://malaria.ourexperiment.org/pharmacophore_modelling_

Do you have the time to do this? (Once that's there, we can build a picture of all the actives/inactives we have, plus the current best guesses for ATP4's structure, and can start to build v2 of the model.) After you're done uploading everything, we can close this issue and start this sub-project in earnest.

drc007 commented 9 years ago

An interesting a diverse set of compounds, what is the evidence that they bind to the same site on the protein?

mattodd commented 9 years ago

None. There is some evidence from cross-resistance studies, which I'll collect together and install on the relevant project page when we're up and running. If you can access the Guy PNAS paper I link to there's a nice diagram showing the locations of all the induced resistance mutations known, on a best guess model of the protein. But there's limited evidence thus far. I have been wondering about imperfectly overlapping binding sites. But the diversity of structures is still amazing to me.

murrayfold commented 9 years ago

Just to clarify before I post stuff. Anything and everything I worked on last year can now be uploaded onto the ELN?

It'll take to a few days to get the data up, lab move this weekend and my computer is with the movers. Once it's in the new building it'll have a new IP address so wont be able to access it till I'm cleared to enter the building - I missed the safety induction last week due to holiday.

mattodd commented 9 years ago

No problem Murray on the delay. And post away - Kiaran gives the green light. I suggest once we have everything in once place, and some clarity in where we're up to, we speak with Kiaran by phone briefly.