Background: Virtual screening methods start to be well established as effective approaches to identify hits, candidates and leads for drug discovery research. Among those, structure based virtual screening (SBVS) approaches aim at docking collections of small compounds in the target structure to identify potent compounds. For SBVS, the identification of candidate pockets in protein structures is a key feature, and the recent years have seen increasing interest in developing methods for pocket and cavity detection on protein surfaces.

Computational small-molecule binding site detection has several important applications in the biomedical field. Notable interests are the identification of cavities for structure-based drug discovery or functional annotation of structures. fpocket is a small-molecule pocket detection program, relying on the geometric α-sphere theory. The fpocket web server allows: (i) candidate pocket detection—fpocket; (ii) pocket tracking during molecular dynamics, in order to provide insights into pocket dynamics—mdpocket; and (iii) a transposition of mdpocket to the combined analysis of homologous structures—hpocket. These complementary online tools allow to tackle various questions related to the identification and annotation of functional and allosteric sites, transient pockets and pocket preservation within evolution of structural families. The server and documentation are freely available at http://bioserv.rpbs.univ-paris-diderot.fr/fpocket.