Fpocket

Fpocket detects small-molecule binding pockets on protein surfaces to support structure-based drug discovery and functional annotation of protein structures.

Key Features:

• Geometric Alpha-Sphere Theory: Fpocket uses alpha-sphere–based geometric detection to identify candidate small-molecule binding pockets on protein surfaces.
• Molecular Dynamics Pocket Tracking (mdpocket): mdpocket tracks pocket dynamics during molecular dynamics simulations to characterize pocket stability and conformational changes.
• Homologous Structures Analysis (hpocket): hpocket transposes mdpocket analyses onto homologous structures to assess pocket preservation and conservation.
• Voronoi Tessellation and Modular C Source: Fpocket computes Voronoi tessellation and alpha spheres using the Qhull package and provides modular C source code enabling custom scoring functions and extraction of pocket descriptors.
• Efficiency and Accuracy: Fpocket detects 94% of pockets within the top three ranked from holo proteins and 92% from apo proteins.
• Benchmarking and Descriptor Collection Tools: Complementary tools Tpocket and Dpocket perform benchmarking on known protein–ligand complexes and collect pocket descriptor values across protein sets.

Scientific Applications:

• Structure-Based Drug Discovery: Identification of candidate binding sites to support virtual screening and ligand design.
• Functional Annotation: Pinpointing functional and allosteric sites on protein structures for annotation of protein function.
• Evolutionary Studies: Analysis of pocket conservation across homologous proteins to study evolutionary pressures and structural adaptation.
• Transient Pocket Analysis: Detection and characterization of transient binding sites that emerge during protein conformational dynamics.

Methodology:

Alpha-sphere–based pocket detection and Voronoi tessellation computed with Qhull, molecular dynamics pocket tracking via mdpocket, homologous-structure transposition via hpocket, and benchmarking/descriptor collection via Tpocket and Dpocket, with modular implementation in C for custom scoring and descriptor extraction.