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 :)
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.
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.
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.
In terms of monomolecular carriers, cyclodextrines have shown moderate success.
Calixarenes offer a more chemically-tunable alternative.
Calixarenes offer a more chemically-tunable alternative.
We decided to go with drugs for the treatment of chronic myeloid leukemia
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
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.
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)
GTP was a small place to start (chemical space blocked due to animation lost in translation)
Interaction energies obtained
Interaction energies obtained
Hydrogen bonds and pi - pi interactions account for the large interaction energies
Hydrogen bonds and pi – pi interactions account for the large interaction energies
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Detail of the interactions in some of the obtained geometries

 

 

MD simulations show the progress of the "release" process.
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)
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.
Chemical space increased regard to the one used with GTP.
In both cases, two insertion modes were considered.
In both cases, two insertion modes were considered.
Some results...
Some results…
100ns of MD show three kinds of structures (inserted, partially released and totally released)
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.
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?
Where do we go from here?
Second generation CML drugs; however Bosutinib poses a funny challenge
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??
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.
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.
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)
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) Any questions?
(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!

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