A Fast Method To Predict Protein Interaction Sites From Sequences

A simple method for predicting residues involved in protein interaction sites is
proposed. In the absence of any structural report, the procedure identifies
linear stretches of sequences as "receptor-binding domains" (RBDs) by analysing
hydrophobicity distribution. The sequences of two databases of non-homologous
interaction sites eliciting various biological activities were tested; 59-80 %
were detected as RBDs. A statistical analysis of amino acid frequencies was
carried out in known interaction sites and in predicted RBDs. RBDs were predicted
from the 80,000 sequences of the Swissprot database. In both cases, arginine is
the most frequently occurring residue. The RBD procedure can also detect residues
involved in specific interaction sites such as the DNA-binding (95 % detected)
and Ca-binding domains (83 % detected). We report two recent analyses; from the
prediction of RBDs in sequences to the experimental demonstration of the
functional activities. The examples concern a retroviral Gag protein and a
penicillin-binding protein. We support that this method is a quick way to predict
protein interaction sites from sequences and is helpful for guiding experiments
such as site-specific mutageneses, two-hybrid systems or the synthesis of
inhibitors.