Molecular complexes at a glance: automated generation of two-dimensional complex diagrams

TLDR

Complex diagrams depict ligands, interacting protein residues, and hydrophilic contacts, and are widely used in structural biology, biochemistry, and medicinal chemistry. The paper presents an algorithm that automatically generates structure diagrams of molecular complexes. The algorithm employs combinatorial optimization to non‑heuristically solve layout problems, represents molecules according to chemical nomenclature, and was evaluated on 305 protein‑ligand complexes, with a webservice implementation. PoseView produced collision‑free layouts for more than three quarters of the tested complexes.

Abstract

In this paper a new algorithmic approach is presented, which automatically generates structure diagrams of molecular complexes. A complex diagram contains the ligand, the amino acids of the protein interacting with the ligand and the hydrophilic interactions schematized as dashed lines between the corresponding atoms. The algorithm is based on a combinatorial optimization strategy which solves parts of the layout problem non-heuristically. The depicted molecules are represented as structure diagrams according to the chemical nomenclature. Due to the frequent usage of complex diagrams in the scientific literature as well as in text books dealing with structural biology, biochemistry and medicinal chemistry, the new algorithm is a key element for computer applications in these areas.The method was implemented in the new software tool PoseView. It was tested on a representative dataset containing 305 protein-ligand complexes in total from the Brookhaven Protein Data Bank. PoseView was able to find collision-free layouts for more than three quarters of all complexes. In the following the layout generation algorithm is presented and, additional to the statistical results, representative test cases demonstrating the challenges of the layout generation will be discussed.The method is available as a webservice at http://www.zbh.uni-hamburg.de/poseview.