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WATOC 2014 – Virtual edition
I had a blast last week at WATOC2014 in Santiago de Chile! It was a wonderful opportunity to find old friends, meet new ones and listen to some exciting research done around the world, as well as some of the classics such as Pekka Pyykkö, who was awarded the Schrödinger medal. I decided to share my talk on SlideShare.com but also here because I found at WATOC that many many people seem to like this little space of mine! I was shocked, flattered but mostly happy to know that this little blog of mine is well regarded.
So, without further ado, here is my presentation at WATOC2014, please read the captions on each image for context. Feel free to make any comments, sharing or liking. Thanks for clicking!
Self explanatory 🙂
Administration of a drug follows one of these two extreme pharmacokinetic pathways. Either way, drugs accumulate in non-target tissues, are wasted and cause undesired secondary effects.
Ideally, a drug should arrive to the target tissue. Several polymolecular drug carriers have been developed.
In terms of monomolecular carriers, cyclodextrines have shown moderate success.
Calixarenes offer a more chemically-tunable alternative.
We decided to go with drugs for the treatment of chronic myeloid leukemia
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Interaction energies were calculated with the NBODel approach, in which elements of the Fock Matrix common to two molecular fragments are deleted
This deletion yields a new Fock matrix which is re-diagonalized; the increase in energy is ascribed to the interaction between both fragments.
GTP was a small place to start (chemical space blocked due to animation lost in translation)
Interaction energies obtained
Hydrogen bonds and pi – pi interactions account for the large interaction energies
Detail of the interactions in some of the obtained geometries
MD simulations show the progress of the “release” process.
So we moved to a larger drug with more degrees of freedom (and a comercial one too)
Chemical space increased regard to the one used with GTP.
In both cases, two insertion modes were considered.
Some results…
100ns of MD show three kinds of structures (inserted, partially released and totally released)
PMF US – the profile of release tells us if the carrier is way too strong to be a carrier at all.
Where do we go from here?
Second generation CML drugs; however Bosutinib poses a funny challenge
A comercial error has released two isomers to the market, only one of them actually works. CAN WE GENERATE A RECOGNITION AGENT??
I know, some results need some attention, I know, trust me.
Also, Imatinib is cardiotoxic. We research now the competence between allegedly affected enzymes and the carriers to at least delay the toxic effect.
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Thanks to all of these wonderful guys who made all publications possible (and also those who gave the money)
(The view from my office in Toluca, Mexico) ANY QUESTIONS? Write it in the comments section!
If you made it this far, let me tell you that this is also available at Slideshare.com 🙂
Thanks for reading, commenting and sharing!
WATOC 2014
I inexcusably forgot to write about my visit to WATOC2014 but as they say it’s better late than never. I’ve been here in Santiago de Chile for a day and a half now attending mostly to session 5 “applications to compelling problems”. WATOC (World Association of Theoretical and Computational Chemists) is probably the largest conference in our speciality and some of the big names are here which makes me very nervous to present my talk!
My talk will be very similar to the one presented in the last ACS meeting in San Francisco, in silico design of monomolecular drug delivery agents based on calix[n]arene macrocycles.
I wont try to report from WATOC, I’m not any good at that but will for sure be available if anyone wants to contact me.
