Fpocket: An open source platform for ligand pocket detection

TLDR

Virtual screening, especially structure‑based virtual screening, is a well‑established method for identifying drug leads, and recent work has focused on detecting pockets and cavities on protein surfaces. Fpocket is an open‑source C‑based pocket detection tool built on Voronoi tessellation and alpha spheres, organized around a central library and three programs—Fpocket, Tpocket, and Dpocket—for pocket identification, benchmarking, and descriptor extraction. Fpocket 1.0 detects 94 % of holo and 92 % of apo protein pockets among the top three ranked pockets, outperforming field standards and running faster, thus providing a rapid, open‑source foundation for further pocket detection and drug‑likability studies. Fpocket is freely available under the GNU GPL license at http://fpocket.sourceforge.net.

Abstract

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.Fpocket is an open source pocket detection package based on Voronoi tessellation and alpha spheres built on top of the publicly available package Qhull. The modular source code is organised around a central library of functions, a basis for three main programs: (i) Fpocket, to perform pocket identification, (ii) Tpocket, to organise pocket detection benchmarking on a set of known protein-ligand complexes, and (iii) Dpocket, to collect pocket descriptor values on a set of proteins. Fpocket is written in the C programming language, which makes it a platform well suited for the scientific community willing to develop new scoring functions and extract various pocket descriptors on a large scale level. Fpocket 1.0, relying on a simple scoring function, is able to detect 94% and 92% of the pockets within the best three ranked pockets from the holo and apo proteins respectively, outperforming the standards of the field, while being faster.Fpocket provides a rapid, open source and stable basis for further developments related to protein pocket detection, efficient pocket descriptor extraction, or drugablity prediction purposes. Fpocket is freely available under the GNU GPL license at http://fpocket.sourceforge.net.