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Posts tagged with "In Silico"

  • In Silico

    Is FEP Ready For the World?

    Here’s a paper that basically throws down the computational gauntlet. A large group of authors from Schrödinger, Nimbus, Columbia, Yale, and UC-Irvine say that their implementation of free energy perturbation (FEP) calculations really does lead to a significant number of more active compounds being predicted. That’s as compared to othe… Read More
  • Drug Assays

    The Old Binding Mode Switcheroo

    When a medicinal chemist gets a promising lead compound, the first thing that’s done to it is to start making modifications to the structure. Add methyls or fluorines, take some of the substituents back off, switch stereochemistry, switch carbons and nitrogens around, that sort of thing. And there you start to build up a structure-activity… Read More
  • In Silico

    Odd Structures, Subjected to Powerful Computations

    Here’s a paper in Nature Chemistry on computational simulation of GPCR activation, using the beta-2 receptor as a model. I’m writing as someone who’s worked on GPCRs, who is interested in such mechanisms, but who is not a computational chemist. And as such, I have some real reservations about the paper. Are my misgivings well-foun… Read More
  • In Silico

    Virtual Covalent Screening

    Covalent drugs have been a big item in R&D over the last few years, and I wrote here about covalent fragments. The whole topic of reactive groups in small molecules and their interaction with living systems and biomolecules is a complicated one, with many interesting twists. Now the Shoichet group at UCSF has what could… Read More
  • Drug Assays

    Compound Properties: Starting a Renunciation

    I’ve been thinking a lot recently about compound properties, and what we use them for. My own opinions on this subject have been changing over the years, and I’m interested to see if I have any company on this. First off, why do we measure things like cLogP, polar surface area, aromatic ring count, and… Read More
  • Drug Development

    More on “Metabolite Likeness” as a Predictor

    A recent computational paper that suggested that similarity to known metabolites could help predict successful drug candidates brought in a lot of comments around here. Now the folks at Cambridge MedChem Consulting have another look at it here. The big concern (as was expressed by some commenters here as well) is the Tanimoto similarity cutoff… Read More
  • Drug Assays

    A New Way to Estimate a Compound’s Chances?

    Just a few days ago we were talking about whether anything could be predicted about a molecule’s toxicity by looking over its biophysical properties. Some have said yes, this is possible (that less polar compounds tend to be more toxic), but a recent paper has said no, that no such correlation exists. This is part… Read More
  • Drug Assays

    We Can’t Calculate Our Way Out of This One

    Clinical trial failure rates are killing us in this industry. I don’t think there’s much disagreement on that – between the drugs that just didn’t work (wrong target, wrong idea) and the ones that turn out to have unexpected safety problems, we incinerate a lot of money. An earlier, cheaper read on either of those… Read More
  • In Silico

    Chemical Space

    I’m listening to Jean-Louis Reymond of Bern talking about the GDB data set, the massive enumerated set of possible molecules. That’s the set of chemically feasible molecules at or below a certain heavy atom count – the first iteration was GDB11 (blogged about here), and it’s since been extended to GDB13, which has nearly one… Read More
  • Clinical Trials

    The Virtual Clinical Trial: Not Quite Around the Corner

    Here’s one of those “Drug Discovery of. . .the. . .Future-ure-ure-ure” articles in the popular press. (I need a reverb chamber to make that work property). At The Atlantic, they’re talking with “medical futurists” and coming up with this: The idea is to combine big data and computer simulations—the kind an engi… Read More