Extraction, Quantification and Visualization of Protein Pockets

Abstract

Molecular surfaces of proteins and other biomolecules, while modeled as smooth analytic interfaces separating the molecule from solvent, often contain a number of pockets, holes and interconnected tunnels with many openings (mouths), aka molecular features in contact with the solvent. Several of these molecular features are biochemically significant as pockets are often active sites for ligand binding or enzymatic reactions, and tunnels are often solvent ion conductance zones. Since pockets or holes or tunnels share similar surface feature visavis their openings (mouths), we shall sometimes refer to these molecular features collectively as generalized pockets or pockets. In this paper we focus on elucidating all these pocket features of a protein (from its atomistic description), via a simple and practical geometric algorithm. We use a two-step level set marching method to compute a volumetric pocket function φ P (x) as the result of an outward and backward propagation. The regions inside pockets can be represented as φ P (x) > 0 and pocket boundaries are computed as the level set φ P (x) = , where > 0 is a small number. The pocket function φ P (x) can be computed efficiently by fast distance transforms. This volumetric representation allows pockets to be analyzed quantitatively and visualized with various techniques. Such feature analysis and quantitative visualization are also generalizable to many other classes of smooth and analytic free-form surfaces or interface boundaries.

Protein PocketViewer: A Web-Service Based Interface for Protein Pocket Extraction and Visualization

“…The protein pocket viewer provides a web-based interface for protein pocket extraction and visualization based on the algorithm in [1]. It was implemented using web services and followed the Model 2 design pattern, consisting of a client web interface for user inputs and visualization, a middle-layer for controlling the flow, and the backend web services performing the actual CPU-intensive computation.…”

“…The Protein Pocket Viewer employs the implementation for protein pocket extraction algorithm described in [1], which was implemented as a C++ program running on a computational server.…”

“…The interface of the web service was defined in the "PocketWS" WSDL file, and implemented as a C++ web service class. The C++ implementation is a thin web service layer that calls upon the existing executable described in [1]with the appropriate arguments. The executable may be updated or replaced, without affecting the rest components of the PPV.…”

“…In this paper, we developed a web service [4] based visualization interface to the pocket extraction algorithm described in [1].The algorithm employs a two-step level set marching algorithm (Fig 1). The first step of the level set marching algorithm marches outward from the protein surface to some distance equal to a given threshold.…”

“…These pocket or tunnel regions are significant because they indicate areas of ligand binding or enzymatic reactions, and tunnels are often solvent ion conductance areas. The Protein Pocket Viewer (PPV) is a web interface that allows the user to extract and visualize the protein pockets in a browser, based on the algorithm in [1]. The PPV packaged the pocket extraction executable as a web service, and made it accessible to all users with the Internet access and a modern java enabled browser.…”