BMaps: A Web Application for Fragment-Based Drug Design and Compound Binding Evaluation

Fragment-based drug design uses data about where, andhow strongly,small chemical fragments bind to proteins, to assemble new drug molecules.Over the past decade, we have been successfully using fragment data,derived from thermodynamically rigorous Monte Carlo fragment-proteinbinding simulations, in dozens of preclinical drug programs. However,this approach has not been available to the broader research communitybecause of the cost and complexity of doing simulations and usingdesign tools. We have developed a web application, called BMaps, tomake fragment-based drug design widely available with greatly simplifieduser interfaces. BMaps provides access to a large repository (>550)of proteins with 100s of precomputed fragment maps, druggable hotspots, and high-quality water maps. Users can also employ their ownstructures or those from the Protein Data Bank and AlphaFold DB. Multigigabytedata sets are searched to find fragments in bondable orientations,ranked by a binding-free energy metric. The designers use this toselect modifications that improve affinity and other properties. BMapsis unique in combining conventional tools such as docking and energyminimization with fragment-based design, in a very easy to use andautomated web application. The service is available at https://www.boltzmannmaps.com.

Automated summary

Fragment-based drug design utilizes data on the binding of small chemical fragments to proteins to create new drug molecules. A web application called BMaps has been developed to make this approach widely accessible through simplified user interfaces. BMaps provides access to a large repository of proteins, precomputed fragment maps, druggable hotspots, and water maps, and allows users to use their own structures or those from external databases. This approach combines conventional tools with fragment-based design in an easy-to-use automated web application. Rating: 8/10