Practical Fragments

Halogen bonds (or X-bonds) are one of the less appreciated protein-ligand interactions. As we discussed in 2022, the polarized nature of a ...

Migraines are the third leading cause of disability worldwide. Although the pathology is complex, blocking the interaction of calcitonin gen...

Accurately and reliably predicting fragment binding modes would be preferrable to doing messy, expensive, and sometimes tedious experimental...

The twin rise of make-on-demand libraries and speedy in silico docking has supercharged fragment screening and optimization: we’ve written p...

Four of the six approved fragment-derived drugs are kinase inhibitors, and three of these bind in the active site. Despite these successes,...

Linking two weak fragments to get a potent binder is something many of us hope for. Unfortunately, as a poll taken a few years back indicat...

COVID-19 will be with us for some time. Despite the unprecedented speed of vaccine development, it is worth remembering that humanity has on...

Despite advances in crystallography , obtaining structures of fragments bound to proteins is still often elusive. Computational docking is ...

In case you missed it, I spoke at the ACS on Sunday.  It was in a computational session looking at designing libraries and I am pretty sure...

Most drugs interact non-covalently with their target. The conventional wisdom was that covalent drugs – especially irreversible ones – wo...

Dan and I blog here because we love it; we don't get paid, it takes a lot of time, and has very little reward.  I love it when I meet s...

Epigenetics is one of the hot new areas for drug research.  It seems like every company has several targets among the bevy of readers, writ...

I recently returned from Philadelphia, where the American Chemical Society held its 244 th national fall meeting. As always this was a ma...

The mobility of proteins is a constant source of wonder. I enjoy looking at experimentally-determined structures of small molecules bound ...

A few weeks ago, we highlighted a paper from Brian Shoichet’s group at UCSF demonstrating that computational screening could successfully ...

I’ve always been something of an empiricist, and have therefore been wary of computational fragment screening. It’s not that I think it’s im...