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Can you give examples of medicines developed thanks to computational chemistry simulations? I'm rather ignorant about this area of research, but it always seem

Can you give examples of medicines developed thanks to computational chemistry simulations? I'm rather ignorant about this area of research, but it always seemed to me kinda fruitless? Sorta like high throughput screening - a ton of resources and computation is dedicated because it sounds like a good idea... but ultimately there is very little to show for it all. Way too little signal and way too much noise.

akiselev 13y ago
http://en.wikipedia.org/wiki/Drug_design#Rational_drug_discovery http://en.wikipedia.org/wiki/Drug_design#Rational_drug_disco... Scroll down to Examples.
- sp332 13y ago
  Why not just link there? https://en.wikipedia.org/wiki/Drug_design#Examples https://en.wikipedia.org/wiki/Drug_design#Examples
cma 13y ago
I'm not giving you what you want, but here's a visual example of using a computational microscope to understand how drug actually works and finds its binding site: http://www.youtube.com/watch?v=PGqCeSjNuTY&t=50m27s http://www.youtube.com/watch?v=PGqCeSjNuTY&t=50m27s If you can't see a difference between that and say, X-Ray crystallography then well..
caycep 13y ago
I would be interested in seeing publications on this - the last time I checked, I think the algorithms and software were being treated as in-house intellectual property by pfizer, novartis, and co
- rotskoff 13y ago
  Actually, the "algorithms" are usually fairly straight-forward and well documented integrators for Newtonian dynamics, usually some form of Verlet Integration. The most popular and efficient Molecular Dynamics packages are open source, some GPL (e.g., NAMD, Gromacs). The technology is nowhere near in silico drug design, but we're converging on useful tools to measure important quantities like free energies of binding. Pharmaceutical companies have some interest in this technology, but at this point, don't direct too much effort into atomistic simulations.
  - caycep 13y ago
    ah thanks. My only experience with this was going to a lecture back in school when they brought in someone from Pfizer's in-house modeling team, but the presentation was a bit light on references/citations...
nl 13y ago
There are lots, and a quick Google search would have cured your unnecessary scepticism. It would be more surprising if this method didn't work than that it does. Imatinib[1] is a good, and pretty old example: Imatinib was developed by rational drug design. After the Philadelphia chromosome mutation and hyperactive bcr-abl protein were discovered, the investigators screened chemical libraries to find a drug that would inhibit that protein. With high-throughput screening, they identified 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib [1] https://en.wikipedia.org/wiki/Imatinib#History https://en.wikipedia.org/wiki/Imatinib#History
- bdcs 13y ago
  Your example is about experimental HTS, not computational simulations which the parent requested.

akiselev 13y ago

http://en.wikipedia.org/wiki/Drug_design#Rational_drug_discovery http://en.wikipedia.org/wiki/Drug_design#Rational_drug_disco... Scroll down to Examples.

sp332 13y ago
Why not just link there? https://en.wikipedia.org/wiki/Drug_design#Examples https://en.wikipedia.org/wiki/Drug_design#Examples

cma 13y ago

I'm not giving you what you want, but here's a visual example of using a computational microscope to understand how drug actually works and finds its binding site: http://www.youtube.com/watch?v=PGqCeSjNuTY&t=50m27s http://www.youtube.com/watch?v=PGqCeSjNuTY&t=50m27s If you can't see a difference between that and say, X-Ray crystallography then well..

caycep 13y ago

I would be interested in seeing publications on this - the last time I checked, I think the algorithms and software were being treated as in-house intellectual property by pfizer, novartis, and co

rotskoff 13y ago
Actually, the "algorithms" are usually fairly straight-forward and well documented integrators for Newtonian dynamics, usually some form of Verlet Integration. The most popular and efficient Molecular Dynamics packages are open source, some GPL (e.g., NAMD, Gromacs). The technology is nowhere near in silico drug design, but we're converging on useful tools to measure important quantities like free energies of binding. Pharmaceutical companies have some interest in this technology, but at this point, don't direct too much effort into atomistic simulations.
- caycep 13y ago
  ah thanks. My only experience with this was going to a lecture back in school when they brought in someone from Pfizer's in-house modeling team, but the presentation was a bit light on references/citations...

nl 13y ago

There are lots, and a quick Google search would have cured your unnecessary scepticism. It would be more surprising if this method didn't work than that it does. Imatinib[1] is a good, and pretty old example: Imatinib was developed by rational drug design. After the Philadelphia chromosome mutation and hyperactive bcr-abl protein were discovered, the investigators screened chemical libraries to find a drug that would inhibit that protein. With high-throughput screening, they identified 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib [1] https://en.wikipedia.org/wiki/Imatinib#History https://en.wikipedia.org/wiki/Imatinib#History

bdcs 13y ago
Your example is about experimental HTS, not computational simulations which the parent requested.