Paper

MAGPIE: an interactive tool for visualizing and analyzing protein-ligand interactions

Weber, Kyle C, Pineda Rodriguez, Daniel C, Sundberg, Belen, Glasgow, Anum

2024

Overview

Quantitative tools to compile and analyze biomolecular interactions among chemically diverse binding partners would improve therapeutics design and aid in the study of molecular evolution. Here we present MAGPIE (Mapping Areas of Genetic Parsimony In Epitopes), a publicly available software package for simultaneously visualizing and analyzing thousands of interactions between a single protein or small molecule ligand (the \"target\") and all of its protein binding partners (\"binders\"). MAGPIE generates an interactive 3D visualization from a set of protein complex structures that share the target ligand, as well as sequence logo-style amino acid frequency graphs that show all the amino acids from the set of protein binders that interact with user-defined target ligand positions or chemical groups. MAGPIE highlights all the salt bridge and hydrogen bond interactions made by the target in the visualization and as separate amino acid frequency graphs. Finally, MAGPIE collates the most common target-binder interactions as a list of \"hotspots,\" which can be used to analyze trends or guide the de novo design of protein binders. As an example of the utility of the program, we used MAGPIE to probe how two ligands bind orthologs of a well-conserved glycolytic enzyme for a detailed understanding of evolutionarily conserved interactions involved in its activation and inhibition. MAGPIE is implemented in Python 3 and freely available at https://github.com/glasgowlab/MAGPIE, along with sample datasets, usage examples, and helper scripts to prepare input structures.Competing Interest StatementThe authors have declared no competing interest.Footnotes* We expanded MAGPIE to include several additional features and added helper scripts to prepare input structures. We fleshed out the manuscript to include these updates, as well as our application of MAGPIE to explore how bacterial orthologs of the glycolytic enzyme phosphofructokinase-1 can interact with allosteric ligands.* https://colab.research.google.com/github/glasgowlab/MAGPIE/blob/GoogleColab/MAGPIE_COLAB.ipynb

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Allosteric properties / Amino acid sequence / Biophysics / Enzymes / Epitope mapping / Gene mapping / Glycolysis / Ligands / Molecular evolution / Phosphofructokinase / Proteins