The tumour necrosis factor as a mediator of vessel inflammation: importance of exposed receptor residues for its neutralization.

Background: The analysis of the macromolecular tumour necrosis factor (TNF)-receptor interface helps to understand the antigenicity of this inflammatory protein.

Method: The calculations are based on structural data from the protein database. The residues of the macromolecular interface are identified in the interface contact matrix, a plot of pair-wise interactions between adjacent residues in the TNF-receptor complex. Starting from the matrix elements, the most exposed residues of the receptor, together with their relative contribution to the interface, are determined. This is done by Voronoi tessellation, a unique and well defined partition of the protein into polyhedral cells defining the proprietary space of the associated amino acid and its contact faces with neighboured residue cells.

Results: Several interfacial receptor residues, contributing with a total amount of 63% to the macromolecular interface, could be identified.

Conclusion: Based on the assumption that residues with higher interfacial exposure values are playing the most important role in TNF-receptor complex, they will be the original material for further developments in engineering more efficient TNF blockers.