ProtoFold Neighborhood Inspector

TL;DR

The paper introduces the ProtoFold Neighborhood Inspector, a visualization tool that helps analyze protein residue neighborhoods to understand the impact of post-translational modifications on protein function and pathogenicity.

Contribution

It presents the Residue Constellation visualization idiom for comparing 3D residue neighborhoods using 2D representations, aiding in PTM analysis.

Findings

Identified patterns in PTM distribution related to pathogenicity.

Demonstrated the effectiveness of the visualization system in protein analysis.

Provided insights into residue neighborhood characteristics.

Abstract

Post-translational modifications (PTMs) affecting a protein's residues (amino acids) can disturb its function, leading to illness. Whether or not a PTM is pathogenic depends on its type and the status of neighboring residues. In this paper, we present the ProtoFold Neighborhood Inspector (PFNI), a visualization system for analyzing residues neighborhoods. The main contribution is a visualization idiom, the Residue Constellation (RC), for identifying and comparing three-dimensional neighborhoods based on per-residue features and spatial characteristics. The RC leverages two-dimensional representations of the protein's three-dimensional structure to overcome problems like occlusion, easing the analysis of neighborhoods that often have complicated spatial arrangements. Using the PFNI, we explored proteins' structural PTM data, which allowed us to identify patterns in the distribution and quantity of per-neighborhood PTMs that might be related to their pathogenic status. In the following, we define the tasks that guided the development of the PFNI and describe the data sources we derived and used. Then, we introduce the PFNI and illustrate its usage through an example of an analysis workflow. We conclude by reflecting on preliminary findings obtained while using the tool on the provided data and future directions concerning the development of the PFNI.