Aromatic-Aromatic Interactions Database (A2ID) Version 2.0

An online repository of aromatic-aromatic interactions in proteins.
Last update on 31, March 2024

Proteins

Networks

Introduction

Introduction

The first version of Aromatic-Aromatic Interaction Database(A2ID): Chourasia, M.; Sastry, G. M.; Sastry, G. N. Int. J. Biol. Macromol. 2011, 48, 540-552.
DOI: 10.1016/j.ijbiomac.2011.01.008

       Aromatic-aromatic interactions are extremely important in controlling the structure and function of biomacromolecules in general and proteins in particular. The orientation of aromatic residues and their arrangement in the proteins illustrates the hidden cache responsible for structural stability. To the best of our knowledge we haven't come cross any systematic analysis on the occurrence of π-π motifs at a database level. Here we ventured on undertaking highly systematic approach to estimate the occurrence of π-π motifs in proteins.

       Geometrical analysis of adjacent aromatic rings of tryptophan (Trp), tyrosine (Tyr), phenylalanine (Phe), and histidine (His) of protein database was done. For this purpose five different classifiers SCOP (Structural Classification of Proteins), CATH (Class (C), Architecture (A), Topology (T) and Homologous superfamily (H)), EC (Enzyme Classification), SCOP2 (SCOP version2), and ECOD (Evolutionary Classification Of protein Domains) were considered.

The latest version of Aromatic-Aromatic Interaction Database(A2ID) V2.0: Kumar, Y. B., Kumar, N., Vaikundamani, S., Nagamani, S., Mahanta, H. J., Sastry, G. M., & Sastry, G. N. (2023). Analyzing the aromatic-aromatic interactions in proteins: A2ID 2.0. International Journal of Biological Macromolecules, 253, 127207.
DOI: 10.1016/j.ijbiomac.2023.127207

About Cut-off Radius

About Cut-off Radius

The protein is scanned from N-terminal to C-terminal to identify an aromatic ring and then the centroid of the ring is computed. Taking the centroid as origin, a virtual sphere of a defined cut-off radius is constructed to find more aromatic rings in the sphere to efine the aromatic networks.

The lower cut-off has been set at 2.5 Å to distinguish between the two centroids of tryptophan (TRP), to treat both of them as independent rings. The cut-off radius (R) values hence range from 3.0 Å to 8.0 Å by a standard increase of 0.5 Å to identify all the exclusive π-π networks.
About π-π Networks

About π-π Networks

A network is defined as a 2π network if the program (based on the distance criteria) could locate the centriod of another aromatic residue within a given cut-off radius. It is further defined as a 3π network if the centroid of another aromatic ring is located within the cut-off distances of either the first or second ring. This process is continued until the program can no longer find an additional aromatic ring in the cut-off radius.

In a given nπ network, the connectivity information indicates the number of connections an aromatic residue has in the whole network. For example, the given connectivity pattern '13211' corresponding to the centroids 'C1C2C3C4C5' of a 5π network indicates that the centroid of the first ring is connected to only one aromatic ring, the second is connected to three rings, the third is connected to 2 rings, while the fourth and fifth rings in the network are connected to one aromatic ring each.
Classification Schemes

Classification & Overlap of Proteins



The distribution of aromatic residues, i.e., tryptophan (TRP), tyrosine (TYR), phenylalanine (PHE), and histidine (HIS), as well as the π-π networks (1 to 4 π) in the proteins across various classification schemes, have been presented in the figure.

The considered classification schemes are SCOP (Structural Classification of Proteins), CATH (Class (C), Architecture (A), Topology (T) and Homologous superfamily (H)), EC (Enzyme Classification), SCOP2 (SCOP version2), and ECOD (Evolutionary Classification Of protein Domains).