Network theory applied to protein structures provides insights into numerous problems of biological relevance. The explosion in structural data available from PDB and simulations establishes a need to introduce a standalone-efficient program that assembles network concepts=parameters under one hood in an automated manner. Herein, we discuss the development=application of an exhaustive, user-friendly, standalone program package named PSN-Ensemble, which can handle structural ensembles generated through molecular dynamics (MD) simulation=NMR studies or from multiple X-ray structures. The novelty in network construction lies in the explicit consideration of side-chain interactions among amino acids. The program evaluates network parameters dealing with topological organization and long-range allosteric communication. The introduction of a flexible weighing scheme in terms of residue pairwise cross-correlation=interaction energy in PSN-Ensemble brings in dynamical=chemical knowledge into the network representation. Also, the results are mapped on a graphical display of the structure, allowing an easy access of network analysis to a general biological community. The potential of PSN-Ensemble toward examining structural ensemble is exemplified using MD trajectories of an ubiquitin-conjugating enzyme (UbcH5b). Furthermore, insights derived from network parameters evaluated using PSN-Ensemble for single-static structures of active=inactive states of b2-adrenergic receptor and the ternary tRNA complexes of tyrosyl tRNA synthetases (from organisms across kingdoms) are discussed. PSN-Ensemble is freely available from http:==vishgraph.mbu.iisc.ernet.in=PSN-Ensemble=psn_index.html.Keywords: PSN-Ensemble program; network features; protein structure network; weighted network; MD=NMR ensemble; UbcH5b; beta2-adrenergic receptor; tRNA synthetasesThe three-dimensional structural organization in proteins can be easily translated into a network, retaining all critical interaction information. PSNEnsemble serves as a robust, standalone program, which can easily compute the network features from a protein structure in an automated and userfriendly manner. The major goal of PSN-Ensemble is to bridge the gap between obtaining important biological information from structural=experimental data Moitrayee Bhattacharyya's current address is Molecular and