Analyzing the aromatic-aromatic interactions in proteins: A²ID 2.0

Area of Science:

• Structural Biology
• Bioinformatics
• Computational Chemistry

Background:

• Aromatic-aromatic (π-π) interactions are crucial in protein structure and function.
• The Aromatic-Aromatic Interactions Database (A²ID) previously documented these interactions.
• Previous versions of A²ID have been reported since 2011.

Purpose of the Study:

• To present the updated Aromatic-Aromatic Interactions Database (A²ID) with an expanded dataset and enhanced analytical capabilities.
• To analyze the characteristics and prevalence of π-π networks in experimentally determined protein structures.
• To provide a comprehensive resource for researchers studying protein structural motifs.

Main Methods:

• Identification and characterization of π-π networks using geometrical parameters like centroid-centroid distances (r) and interplanar angles (ϕ).
• Analysis of over 3.4 million π-π networks from 84,500 protein structures.
• Integration of SCOP2 and ECOD classifiers alongside existing SCOP, CATH, and EC classifications for broader analysis.

Main Results:

• The current A²ID version contains 3,444,619 π-π networks.
• Approximately 92.50% of instances are either 2π (77.34%) or 3π (15.23%) networks.
• Phenylalanine (PHE) and Tyrosine (TYR) residues are the most common interacting pairs in 2π networks.

Conclusions:

• The updated A²ID provides an extensive and detailed resource for studying protein aromatic interactions.
• The prevalence of smaller π-π networks (2π and 3π) highlights their significance in protein architecture.
• Expanded classification systems enable multi-perspective exploration of π-π network characteristics and functional roles.