TRAPP webserver: predicting protein binding site flexibility and detecting transient binding pockets.

Abstract

The TRAnsient Pockets in Proteins (TRAPP) webserver provides an automated workflow that allows users to explore the dynamics of a protein binding site and to detect pockets or sub-pockets that may transiently open due to protein internal motion. These transient or cryptic sub-pockets may be of interest in the design and optimization of small molecular inhibitors for a protein target of interest. The TRAPP workflow consists of the following three modules: (i) TRAPP structure— generation of an ensemble of structures using one or more of four possible molecular simulation methods; (ii) TRAPP analysis—superposition and clustering of the binding site conformations either in an ensemble of structures generated in step (i) or in PDB structures or trajectories uploaded by the user; and (iii) TRAPP pocket—detection, analysis, and visualization of the binding pocket dynamics and characteristics, such as volume, solvent-exposed area or properties of surrounding residues. A standard sequence conservation score per residue or a differential score per residue, for comparing on- and off-targets, can be calculated and displayed on the binding pocket for an uploaded multiple sequence alignment file, and known protein sequence annotations can be displayed simultaneously. The TRAPP webserver is freely available at http://trapp.h-its.org.