The fidelity of biological processes and reactions, inspite of the widespread diversity, is programmed by highly specific physico-chemical principles. This underlines our basic understanding of different interesting phenomena of biological relevance, ranging from enzyme specificity to allosteric communication, from selection of fold to structural organization / states of oligomerization, from half-sites-reactivity to reshuffling of the conformational free energy landscape, encompassing the dogma of sequence-structure dynamics-function of macromolecules. The role of striking an optimal balance between rigidity and flexibility in macromolecular 3D structural organisation is yet another concept that needs attention from the functional perspective. Needless to say that the variety of protein structures and conformations naturally leads to the diversity of their function and consequently many other biological functions in general. Classical models of allostery like the ‘MWC model’ or the ‘KNF model’ and the more recently proposed ‘population shift model’ have advanced our understanding of the underlying principles of long range signal transfer in macromolecules. Extensive studies have also reported the importance of the fold selection and 3D structural organisation in the context of macromolecular function. Also ligand induced conformational changes in macromolecules, both subtle and drastic, forms the basis for controlling several biological processes in an ordered manner by re-organizing the free energy landscape. The above mentioned biological phenomena have been observed from several different biochemical and biophysical approaches. Although these processes may often seem independent of each other and are associated with regulation of specialized functions in macromolecules, it is worthwhile to investigate if they share any commonality or interdependence at the detailed atomic level of the 3D structural organisation. So the nagging question is, do these diverse biological processes have a unifying theme, when probed at a level that takes into account even subtle re-orchestrations of the interactions and energetics at the protein/nucleic acid side-chain level. This is a complex problem to address and here we have made attempts to examine this problem using computational tools. Two methods have been extensively applied: Molecular Dynamics (MD) simulations and network theory and related parameters. Network theory has been extensively used in the past in several studies, ranging from analysis of social networks to systems level networks in biology (e.g., metabolic networks) and have also found applications in the varied fields of physics, economics, cartography and psychology. More recently, this concept has been applied to study the intricate details of the structural organisation in proteins, providing a local view of molecular interactions from a global perspective. On the other hand, MD simulations capture the dynamics of interactions and the conformational space associated with a given state (e.g., different ligand-bound states) of the macromolecule. The unison of these two methods enables the detection and investigation of the energetic and geometric re-arrangements of the 3D structural organisation of macromolecule/macromolecular complexes from a dynamical or ensemble perspective and this has been one of the thrust areas of the current study. So we not only correlate structure and functions in terms of subtle changes in interactions but also bring in conformational dynamics into the picture by studying such changes along the MD ensemble. The focus was to identify the subtle rearrangements of interactions between non-covalently interacting partners in proteins and the interacting nucleic acids. We propose that these rearrangements in interactions between residues (amino acids in proteins, nucleic acids in RNA/DNA) form the common basis for different biological phenomena which regulates several apparently unrelated processes in biology. Broadly, the major goal of this work is to elucidate the physico-chemical principles underlying some of the important biological phenomena, such as allosteric communication, ligand induced modulation of rigidity/flexibility, half-sites-reactivity and so on, in molecular details. We have investigated several proteins, protein-RNA/DNA complexes to formulate general methodologies to address these questions from a molecular perspective. In the process we have also specifically illuminated upon the mechanistic aspects of the aminoacylation reaction by aminoacyl-tRNA synthetases like tryptophanyl and pyrrolysyl tRNA synthetase, structural details related to an enzyme catalyzed reaction that influences the process of quorum sensing in bacteria. Further, we have also examined the ‘dynamic allosterism’ that manipulates the activity of MutS, a prominent component of the DNA bp ‘mismatch repair’ machinery. Additionally, our protein structure network (PSN) based studies on a dataset of Rossmann fold containing proteins have provided insights into the structural signatures that drive the adoption of a fold from a repertoire of diverse sequences. Ligand induced percolations distant from the active sites, which may be of functional relevance have also been probed, in the context of the S1A family of serine proteases. In the course of our investigation, we have borrowed several concepts of network parameters from social network analysis and have developed new concepts. The Introduction (Chapter-1) summarizes the relevant literature and lays down a suitable background for the subsequent chapters in the thesis. The major questions addressed and the main goal of this thesis are described to set an appropriate stage for the detailed discussions. The methodologies involved are discussed in Chapter-2. Chapter-3 deals with a protein, LuxS that is involved in the bacterial quorum sensing; the first part of the chapter describes the application of network analysis on the static structures of several LuxS proteins from different organisms and the second part of this chapter describes the application of a dynamic network approach to analyze the MD trajectories of H.pylori LuxS. Chapter-4 focuses on the investigation of human tryptophanyl-tRNA synthetase (hTrpRS), with an emphasis to identify ligand induced subtle conformational changes in terms of the alternation of rigidity/flexibility at different sites and the re-organisation of the free energy landscape. Chapter-5 presents a novel application of a quantum clustering (QC) technique, popular in the fields of pattern recognition, to objectively cluster the conformations, sampled by molecular dynamics simulations performed on different ligand bound structures of the protein. The protein structure network (PSN) in the earlier studies were constituted on the basis of geometric interactions. In Chapters 6 and 7, we describe the networks (proteins+nucleic acids) using interaction energy as edges, thus incorporating the detailed chemistry in terms of an energy-weighted complex network. Chapter-6 describes an application of the energy weighted network formalism to probe allosteric communication in D.hafniense pyrrolysyl-tRNA synthetase. The methodology developed for in-depth study of ligand induced changes in DhPylRS has been adopted to the protein MutS, the first ‘check-point protein’ for DNA base pair (bp) mismatch repair. In Chapter-7, we describe the network analysis and the biological insights derived from this study (the work is done in collaboration with Prof. David Beveridge and Dr. Susan Pieniazek). Chapter-8 describes the application of a network approach to capture the ligand-induced subtle global changes in protein structures, using a dataset of high resolution structures from the S1A family of serine proteases. Chapter-9 deals with probing the structural rationale behind diverse sequences adopting the same fold with the NAD(P)-binding Rossmann fold as a case study. Future directions are discussed in the final chapter of the thesis (Chapter-10).