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Posts tagged with "In Silico"

  • In Silico

    Standards of Proof

    Here are some slides from Anthony Nicholls of OpenEye, from his recent presentation here in Cambridge on his problems with molecular dynamics calcuations. Here’s his cri du coeur (note: fixed a French typo from the original post there): . . .as a technique MD has many attractive attributes that have nothing to do with its… Read More
  • Chemical News

    Low Energy Records

    Pick an empirical formula. Now, what’s the most stable compound that fits it? Not an easy question, for sure, and it’s the topic of this paper in Angewandte Chemie. Most chemists will immediately realize that the first problem is the sheer number of possibilities, and the second one is figuring out their energies. A nonscientist… Read More
  • In Silico

    When the “c” in cLogP Stands For “Crazy” (Update: Fixed!)

    I don’t know how many readers out there use the cLogP function in ChemDraw, but you might want to take a look at the illustration here before you use it again. A reader alerted me to this glitch: drawing in explicit hydrogens sends it into an even stranger world of fantasy than most calculated logP… Read More
  • In Silico

    Models and Reality

    I have to admit that I enjoyed seeing this question asked: how come we still use wind tunnels in aerodynamic engineering? Why don’t we just model everything in software? The answers, from people who’ve actually done some of the work, are what you might expect: the models all involve degrees of approximation, gloss over some… Read More
  • Drug Assays

    Unraveling An Off-Rate

    Medicinal chemists talk a lot more about residence time and off rate than they used to. It’s become clear that (at least in some cases) a key part of a drug’s action is its kinetic behavior, specifically how quickly it leaves its binding site. You’d think that this would correlate well with its potency, but… Read More
  • In Silico

    Molecular Dynamics, Pro and Con

    Readers will remember the spirited discussion about the usefulness of molecular dynamics in the comments thread to this post. Now Anthony Nicholls of OpenEye Software, who ignited that particular powder train, is going to defend his position in person this Wednesday. There will be a lunchtime seminar and discussion at the OpenEye offices (222 3rd… Read More
  • 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