Reverse fragment based drug discovery approach via simple estimation of fragment contributions

Abstract

Contributions of different fragments of a ligand into the binding/activity to a specified target are of importance to guide hit-to-lead drug discovery, and fragment based drug discovery (FBDD) approach has proven to be quite fruitful. However, the experimental means of FBDD are generally not affordable to many researchers working in the drug discovery field, especially to small medicinal chemistry groups at universities. To partially solve this problem, we propose a Reversed Fragment Based Drug Discovery (R-FBDD) approach in which the contributions of fragments of a molecule are estimated using scoring functions in order to detect whether a fragment is a ‘binding anchor’ or a ballast, thus guiding further development.