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Posts tagged with "In Silico"

  • Biological News

    Allosteric Binding Illuminated?

    G-protein coupled receptors are one of those areas that I used to think I understood, until I understood them better. These things are very far from being on/off light switches mounted in drywall – they have a lot of different signaling mechanisms, and none of them are simple, either. One of those that’s been known… Read More
  • Drug Assays

    More Thoughts on Compound Metrics

    Over at Practical Fragments, Dan Erlanson has comments on the Michael Shultz paper that I wrote about here. He goes into details on some of the problems that turn up when you try to apply various compound metrics across a broad range of molecular weights and/or lipophilicities. In the most obvious example, the indices that… Read More
  • Drug Assays

    Too Many Metrics

    Here’s a new paper from Michael Shultz of Novartis, who is trying to cut through the mass of metrics for new compounds. I cannot resist quoting his opening paragraph, but I do not have a spare two hours to add all the links: Approximately 15 years ago Lipinski et al. published their seminal work linking… Read More
  • Analytical Chemistry

    An HIV Structure Breakthrough? Or “Complete Rubbish”?

    Structural biology needs no introduction for people doing drug discovery. This wasn’t always so. Drugs were discovered back in the days when people used to argue about whether those “receptor” thingies were real objects (as opposed to useful conceptual shorthand), and before anyone had any idea of what an enzyme’s active sit… Read More
  • Drug Development

    Druggability: A Philosophical Investigation

    I had a very interesting email the other day, and my reply to it started getting so long that I thought I’d just turn it into a blog post. Here’s the question: How long can we expect to keep finding new drugs? By way of analogy, consider software development. In general, it’s pretty hard to… Read More
  • Analytical Chemistry

    The 3D Fragment Consortium

    Fragment-based screening comes up here fairly often (and if you’re interested in the field, you should also have Practical Fragments on your reading list). One of the complaints both inside and outside the fragment world is that there are a lot of primary hits that fall into flat/aromatic chemical space (I know that those two… Read More
  • Chemical Biology

    Evolving Enzymes: Let ‘Em Rip

    Evolutionary and genetic processes fascinate many organic chemists, and with good reason. They’ve provided us with the greatest set of chemical catalysts we know of: enzymes, which are a working example of molecular-level nanotechnology, right in front of us. A billion years of random tinkering have accomplished a great deal, but (being human… Read More
  • Drug Assays

    More Whitesides on Ligand Binding

    George Whitesides and his lab have another paper out on the details of how ligands bind to proteins. They’re still using the favorite model enzyme of all time (carbonic anhydrase), the fruit fly and nematode of the protein world. Last time around, using a series of ligands and their analogs with an extra phenyl in… Read More
  • In Silico

    MedChemica: When One Compound Collection Isn’t Enough

    According to SciBx, here’s another crack at computational solutions for drug discovery: MedChemica, a venture started by several ex-AstraZeneca scientists. They’re going to be working with data from both AZ and Roche, using what sounds like a “matched molecular pair” approach: Although other algorithms try to relate structur… Read More
  • Analytical Chemistry

    GPCRs Are As Crazy As You Thought

    That’s my take-away from this paper, which takes a deep look at a reconstituted beta-adrenergic receptor via fluorine NMR. There are at least four distinct states (two inactive ones, the active one, and an intermediate), and the relationships between them are different with every type of ligand that comes in. Even the ones that look… Read More
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