Aromatic–aromatic interactions database, A²ID: an analysis of aromatic π-networks in proteins

Abstract

The geometrical arrangement of the aromatic rings of phenylalanine, tyrosine, tryptophan and histidine has been analyzed at a database level using the X-ray crystal structure of proteins from PDB in order to find out the aromatic–aromatic (π–π) networks in proteins and to understand how these aromatic rings are connected with each-other in a specific π–π network. A stringent examination of the 7848 proteins indicates that close to 89% of the proteins have occurrence of at least a network of 2π or a higher π–π network. The occurrence of π–π networks in various protein superfamilies based on SCOP, CATH and EC classifiers has also been probed in the present work. In general, we find that multidomain and membrane proteins as well as lyases show a more number of these networks. Analysis of the distribution of angle between planes of two proximal aromatic rings (ϕ) distribution indicates that at a larger cutoff distance (between centroid of two aromatic rings), above 5 Å, C–H⋯π interactions (T-shaped orientation) are more prevalent, while π–π interactions (stacked orientation) are more prevalent at a smaller cutoff distance. The connectivity patterns of π–π networks propose strong propensity of finding arrangement of aromatic residues as clusters rather than linear arrangement. We have also made a public domain database “Aromatic–Aromatic Interactions Database” (A²ID) comprising of all types of π–π networks and their connectivity pattern present in proteins. It can be accessed by url http://203.199.182.73/gnsmmg/databases/aidb/aidb.html.