Free Energy Perturbation (FEP): Another technique in the drug discovery toolbox
Introduction When I first started using CHARMM over 20 years ago as a PhD student, I regularly came across references ...
FieldStere v3.0 is scheduled for release at the end of October. This version brings additions to the scientific capabilities as well as many new and improved features to the user interface.
In this version you can score molecules suggested by FieldStere against multiple other actives. This gives the software more flexibility when used on optimization projects because it allows you to enter your series and a high active, specify the part of your molecule that you wish to change or optimize, and view FieldStere’s suggestions for new molecules to make in your series that will mimic the known active. A natural extension of scoring bioisosteres against an alternative chemical series is to enable fragment growing. Given a small, active molecule and a larger, better active, FieldStere can now suggest new functional groups to introduce to grow the smaller molecule. We’re excited about this new feature and have already generated some interesting examples which we will blog on in the next couple of weeks.
Growing fragments with FieldStere: The green fragment above was grown to give bioisosteres of the purple molecule. Both molecules appear in crystal structures of p38-kinase but bound to different protein conformations. The yellow molecule shows one of the results – an imidazole is used to interact with the key hinge binding region.
Our applications have gained a reputation for being extremely easy to use and FieldStere is probably the most intuitive of all. However, we took a look the FieldStere interface and realized that we could do even better. We’ve completely redesigned the wizard interface and tweaked much of the display code in the UI. The final version looks cleaner, uses fewer mouse clicks and brings some of the important but buried science to the fore.
This release will include completely new databases and an automatic database update utility. Alongside databases derived from commercially available compounds, we are aiming to distribute databases based on VEHICLe, Chembl, and in due course, CSD. These databases will access a wider range of chemistries and fragments than are available from the compound suppliers giving you more diversity and novelty in your chemistry space.
Overall FieldStere v3.0 is a major improvement over the current release. We will be rolling out the new release to existing customers in the next couple of weeks. If you are interested in trying the new features for yourself then contact our Sales team for a free evaluation.