Abstract

Background: Large-scale energy landscape characterization of protein-protein interactions (PPIs) is important to understand the interaction mechanism and protein-protein docking methods. The experimental methods for detecting energy landscapes are tedious and the existing computational methods require longer simulation time.

Objective: The objective of the present work is to ascertain the energy profiles at the interface regions in a rapid manner to analyze the energy landscape of protein-protein interactions.

Methods: The atomic coordinates obtained from the X-ray and NMR spectroscopy data are considered as inputs to compute cumulative energy profiles for experimentally validated protein-protein complexes. The energies computed by the program were comparable to the standard molecular dynamics simulations.

Results: The PPI Profiler not only enables rapid generation of energy profiles but also facilitates the detection of hot spot residue atoms involved therein.

Conclusion: The hotspot residues and their computed energies matched with the experimentally determined hot spot residues and their energies which correlated well by employing the MM/GBSA method. The proposed method can be employed to scan entire proteomes across species at an atomic level to study the key PPI interactions.

Keywords: Protein-protein interaction, energy profiles, DFT, energy landscape, hot spot residues, proteomes.

Graphical Abstract