TRAPP

TRAPP identifies and analyzes transient and cryptic binding pockets and sub-pockets in protein structures to characterize binding-site dynamics relevant to ligand interactions and small-molecule inhibitor design.

Key Features:

• Automated workflow: An automated computational workflow systematically explores binding-site dynamics.
• Structure generation module: Generates ensembles of protein conformations using one or more of four distinct molecular simulation methods.
• Analysis and clustering module: Performs structural superposition and clustering of generated structures and accepts PDB structures and trajectory files as input.
• Pocket detection and characterization: Detects transient pockets and sub-pockets and analyzes dynamics and metrics such as pocket volume and solvent-exposed area.
• Sequence conservation scoring: Calculates per-residue sequence conservation scores and differential conservation scores for comparing on- and off-targets and maps these to binding pockets.
• Annotation integration: Integrates known protein sequence annotations with structural and pocket data.

Scientific Applications:

• Drug discovery and development: Identification of cryptic sub-pockets to guide novel small-molecule inhibitor design.
• Protein–ligand interaction analysis: Characterization of binding-site dynamics across multiple conformations to inform binding mechanisms.
• Target selectivity assessment: Use of differential conservation scores and pocket features to compare on- and off-targets for selectivity considerations.

Methodology:

Generation of protein conformational ensembles using up to four molecular simulation methods; structural superposition and clustering of ensembles; detection and analysis of transient pockets with calculation of pocket metrics (volume, solvent-exposed area); calculation of per-residue conservation and differential on-/off-target conservation scores; integration of sequence annotations.