Democratizing computational FBLD with BMaps

Computational approaches to FBLD continue to gain in power. For the most part, they require significant knowledge and installation of expensive, customized software. To remedy this, John Kulp, III and colleagues at Conifer Point Pharmaceuticals have introduced a new web-based application, BMaps, which they describe in a recent J. Chem. Inf. Mod. paper.

 

As the researchers note (and appropriately reference), there are more than a dozen virtual fragment-based design tools and another dozen web-based tools. BMaps (for Boltzmann Maps) aims to provide a full range of functions, from visualizing proteins, finding hot spots, docking fragments, and growing them. It also provides information on the energetics of bound water molecules, which as we’ve written can be crucial players in optimizing protein-ligand interactions.

 

Two key techniques used by BMaps are Grand Canonical Monte Carlo (GCMC) simulations and Simulated Annealing of Chemical Potential (SACP). The first entails comprehensive sampling of different fragment conformations on a protein of interest and assessing binding free energy. The second tool “forcefully inserts fragments into all the binding sites of the protein” and then removes them slowly to evaluate which are most difficult to remove, and thus most tightly bound. Together, GCMC-SACP can be used to evaluate fragment binding to any protein uploaded to the site from the protein data bank, AlphaFold, or any other source.

 

One nice feature of BMaps is a repository of several hundred proteins each with more than 100 fragment and water simulations. BMaps also contains a database of more than 4000 fragments, including MiniFrags. Users can import their own fragments or computationally deconstruct larger ligands. The paper itself is quite short, but the supporting information provides more guidance on how to use the software.

 

The researchers “aim to democratize the availability of accurate fragment and water maps,” a laudable goal. Most computational features are available with a free account, though with restrictions on the number of operations per month.

 

BMaps looks quite powerful and easy to use, but I do wish the researchers had included some full case studies, for example those used by the free FastGrow tool we highlighted last year. Try it out and let the community know what you think!