Mining anion-aromatic interactions in the Protein Data Bank.

Emilia Kuzniak-Glanowska,Andrzej J Bojarski,Rafał Kurczab,Michał Glanowski,Robert Podgajny

doi:10.1039/d2sc00763k

Abstract

Mutual positioning and non-covalent interactions in anion–aromatic motifs are crucial for functional performance of biological systems. In this context, regular, comprehensive Protein Data Bank (PDB) screening that involves various scientific points of view and individual critical analysis is of utmost importance. Analysis of anions in spheres with radii of 5 Å around all 5- and 6-membered aromatic rings allowed us to distinguish 555 259 unique anion–aromatic motifs, including 92 660 structures out of the 171 588 structural files in the PDB. The use of a scarcely exploited (x, h) coordinate system led to (i) identification of three separate areas of motif accumulation: A – over the ring, B – over the ring-substituent bonds, and C – roughly in the plane of the aromatic ring, and (ii) unprecedented simultaneous comparative description of various anion–aromatic motifs located in these areas. Of the various residues considered, i.e. aminoacids, nucleotides, and ligands, the latter two exhibited a considerable tendency to locate in region Avia archetypal anion–π contacts. The applied model not only enabled statistical quantitative analysis of space around the ring, but also enabled discussion of local intermolecular arrangements, as well as detailed sequence and secondary structure analysis, e.g. anion–π interactions in the GNRA tetraloop in RNA and protein helical structures. As a purely practical issue of this work, the new code source for the PDB research was produced, tested and made freely available at https://github.com/chemiczny/PDB_supramolecular_search.

Highlights

Non-covalent interactions that involve anions and aromatic rings have become a focal point in the eld of supramolecular chemistry, as they continue to stimulate the exploration of functional molecular materials and studies of molecular activity in biological systems
Ratio of non-standard to standard (AA, NU) residues increase from region C to region A. This suggests that anion–p interactions are probably important to docking of the ligand and might be essential from a drug design perspective
From sequence and secondary structure analyses, we found that anion–p interactions might in uence GNRA tetraloop thermostability in RNA and on helical structures in proteins

Summary

Introduction

Non-covalent interactions that involve anions and aromatic rings have become a focal point in the eld of supramolecular chemistry, as they continue to stimulate the exploration of functional molecular materials and studies of molecular activity in biological systems. The structure where the anion is located above the aromatic ring and is involved in interactions with both some metal cation and the hydrogen bond is classi ed in groups (i) and (v) simultaneously.

Results

Conclusion