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Posts tagged with "In Silico"

  • In Silico

    Floppiness Is Not Your Friend: Who Knew?

    There’s a trick that every medicinal chemist learns very early, and continues to apply every time its feasible: take two parts of your compound, and tie them together into a ring. The reason that works so well may not be immediately obvious if you’re not a medicinal chemist, so let me expand on them a… Read More
  • General Scientific News

    Protein Folding: Complexity to Make More Complexity?

    Want a hard problem? Something to really keep you challenged? Try protein folding. That’ll eat up all those spare computational cycles you have lounging around and come back to ask for more. And it’ll do the same for your brain cells, too, for that matter. The reason is that a protein of any reasonable size… Read More
  • Analytical Chemistry

    X-Ray Structures: Handle With Care

    X-ray crystallography is wonderful stuff – I think you’ll get chemists to generally agree on that. There’s no other technique that can provide such certainty about the structure of a compound – and for medicinal chemists, it has the invaluable ability to show you a snapshot of your drug candidate bound to its protein target. Read More
  • In Silico

    Up Close and Personal

    Something that’s come up in the last few posts around here is the way that we chemists think about the insides of enzymes. It’s a tricky subject, because when you picture things on that scale, the intuition you have for objects starts to betray you. Consider water. We humans have a pretty good practical understanding… Read More
  • Drug Industry History

    O Pioneers!

    Drug Discovery Today has the first part of an article on the history of the molecular modeling field, this one covering about 1960 to 1990. It’s a for-the-record document, since as time goes on it’ll be increasingly hard to unscramble all the early approaches and players. I think this is true for almost any technology; Read More
  • Analytical Chemistry

    Start Small, Start Right

    There’s an excellent paper in the most recent issue of Chemistry and Biology that illustrates some of what fragment-based drug discovery is all about. The authors (the van Aalten group at Dundee) are looking at a known inhibitor of the enzyme chitinase, a natural product called argifin. It’s an odd-looking thing – five amino acids… Read More
  • Drug Industry History

    Smaller, Wetter, Harder to Work With

    There’s an interesting article coming out in J. Med. Chem. on antibiotic compounds, which highlights something that’s pretty clear if you spend some time looking at the drugs in that area. We make a big deal (or have made one over the last ten years) about drug-like properties – all that Rule-of-Five stuff and its… Read More
  • In Silico

    Melting Keys and Squishy Locks

    Pretty much the only thing that an interested lay person has heard about ligand binding is the “lock and key” metaphor. I’m not saying that you could walk down the sidewalk getting nods of recognition with it, but if someone’s heard anything about how enzymes or receptors work (well, anything correct), that’s probably… Read More
  • Drug Assays

    No Shortcuts

    I wanted to link tonight to the “Milkshake Manifesto” over at OrgPrep Daily. It’s a set of rules for med-chem, and looking them over, I agree with them pretty much across the board. There’s a general theme in them of getting as close to the real system as you can, which is a theme I’ve… Read More
  • In Silico

    Wrong, But Still Convincing

    SciTheory has a post, complete with links to the relevant articles in Science, etc., on a recent batch of trouble in structural biology. Geoffrey Chang and his group at Scripps have been working on the structures of transporter proteins, which sit in the cell membrane and actively move nonpermeable molecules in and out. There are… Read More
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