JEDII: Juxtaposition Enabled DNA-binding Interface Identifier

The specific recognition of small stretches of the genomic sequence by their cognate binding protein partners is crucial for various biological processes. Traditionally the prediction of DNA-protein interactions has been treated as two separate problems - one where we predict the most probable DNA sequence that a given protein would bind to and another where we determine the amino acids constituting the DNA binding pocket on a protein. In this study, we introduce JEDII, a template-based method that combines these two aspects of DNA-protein interactions and predicts the residues, nucleotides and amino acids, that would mediate the interaction. Our computational method utilises known structures of DNA-protein complexes in a protocol that superimposes amino acid-nucleotide hydrogen-bonding donor and acceptors atoms on one another to identify the protein-DNA interface. The corner stone of the method is that specificity bestowing hydrogen-bonding interactions are structurally conserved. We validated the accuracy of our procedure on a dataset of 285 DNA-protein complexes where JEDII predicted the cognate DNA sequence with a 62% accuracy. It predicted the DNA-binding amino acids on the protein with 94 % accuracy and an MCC of 0.70. JEDII was also separately compared to other popular methods that predict the cognate DNA sequence and to methods that predict the DNA binding residues. The comparisons were done over four different datasets and JEDII outperformed most methods over all these data sets. JEDII is a robust method following a simple replicable algorithm to determine the molecular basis of DNA-protein specificity and could be instrumental in predicting DNA-protein complexes that are central to key biological phenomena.