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Posts tagged with "In Silico"

  • Chemical News

    Not Even Wrong

    This paper is not going to make a lot of computational chemists very happy at all. It’s from Dan Singleton and Erik Plata at Texas A&M, and it’s on the Morita-Bayliss-Hillman reaction. More specifically, though, it’s on the many computational attempts to decide on the mechanism of the MBH reaction, and taken together, they… Read More
  • In Silico

    Diversity and Similarity Scoring: Does One Size Ever Fit All?

    We spend a lot of time talking about compound similarities in this business. All those schemes for virtual screening, to find new activities for old compounds, to predict side effects and general toxicity, and many others besides rely on some sort of measurement of how similar various compounds (and collections of compounds) are to each… Read More
  • In Silico

    Neural Networks for Drug Discovery: A Work in Progress

    There have been many attempts over the years to bring together large amounts of biological and drug activity data, winnow them computationally, and come up with insights that would not be obvious to human eyes. It’s a natural thing to imagine – there are so many drug targets in the body, doing so many things… Read More
  • 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