FGDB: a comprehensive graph database of ligand fragments from the Protein Data Bank

Abstract

Abstract This work presents Fragment Graph DataBase (FGDB), a graph database of ligand fragments extracted and generated from the protein entries available in the Protein Data Bank (PDB). FGDB is meant to support and elicit campaigns of fragment-based drug design, by enabling users to query it in order to construct ad hoc, target-specific libraries. In this regard, the database features more than 17 000 fragments, typically small, highly soluble and chemically stable molecules expressed via their canonical Simplified Molecular Input Line Entry System (SMILES) representation. For these fragments, the database provides information related to their contact frequencies with the amino acids, the ligands they are contained in and the proteins the latter bind to. The graph database can be queried via standard web forms and textual searches by a number of identifiers (SMILES, ligand and protein PDB ids) as well as via graphical queries that can be performed against the graph itself, providing users with an intuitive and effective view upon the underlying biological entities. Further search mechanisms via advanced conjunctive/disjunctive/negated textual queries are also possible, in order to allow scientists to look for specific relationships and export their results for further studies. This work also presents two sample use cases where maternal embryonic leucine zipper kinase and mesotrypsin are used as a target, being proteins of high biomedical relevance for the development of cancer therapies. Database URL: http://biochimica3.bio.uniroma3.it/fragments-web/