A Hierarchical Method to Analyze Protein-DNA Interfaces

Abstract

ABSTRACTThe accessibility of genetic information and packaging of long chromosomal DNA into micron-sized nuclei is a great example of protein-DNA interaction. A large number of protein-DNA structures are available in the database and is continuously increasing. The analysis of such huge data to extract meaningful insights, several computational tools such as hydrogen bonding, SASA, all intermolecular heavy atom-to-atom contacts, as well as web-server and databases such as DNAproDB, PDIdb, PDB2PQR, Bio-python are available. Generally, the interaction between the protein and DNA is analyzed based on all heavy atom-to-atom contact matrices which are computationally expensive. Herein, a new and robust hierarchical approach is developed to analyze the protein-DNA interface. The present hierarchical method comprises two steps; the first step is to recognize the protein residue-nucleotide pairs at the interface by employing pairwise distance cut-off between the Cα of the protein residues and 05′ of the nucleotide and the second step is to calculate heavy atom-to-atom contact matrix using the first step as a qualifier. This method reduces the computational cost by three orders of magnitude making it tractable even on personal computers. On the whole, the protein-DNA interface is dominated by the arginine residues with a notable presence of lysine, serine, and tyrosine, highlighting the pivotal role of electrostatic interactions and hydrogen bonding in aggregation.Abstract Figure