Development of a method for selecting fragment candidate combinations for fragment-based drug design

Abstract

In fragment-based drug design (FBDD), active fragments are identified using experimental methods and medicinal chemists combine then to design new compounds to synthesis. Recently, in silico methods are also proposed for fragments identification and following compound design. In silico fragment identification methods may find a number of active fragment candidates on the active site, resulting in the combinatorial explosion of fragment lists that are combined to design new compounds. Therefore computationally inexpensive ways to select fragment lists are required. To find an appropriate threshold for selecting, we try to analyze all the triplets from a fragment library for in silico FBDD against an existing compounds DB and a drug-like compound DB. It shows whether each combination exists in known compounds or compounds with a specified physicochemical property. The result shows that the hit count of substructure search of fragment list against a compound DB may be used as a criterion for fragment list selection.