This work addresses the basic problems of biology and medicinal chemistry. The main focus is to understand structural features and mechanism of therapeutically relevant targets viz. H+K+‐ATPase, Ca2+‐ATPase and DNA with the aid of CADD tools. This includes the comparative study of proteins, their structural differences and the role of pKa of titratable residues in the active site, probing the structural requirement of ligands in order to develop strategies to design new inhibitors and/or to modify known ligands to augment the activity. I analyzed the aromatic networks in membrane proteins to understand the important role played by aromatic residues in transporting cations across the membrane. This study has been extended at database level considering all proteins of Protein Data Bank to find out specific patterns of aromatic‐aromatic networks and their connectivity in proteins. There has been a profound interest in designing the covalent and non‐covalent DNA minor groove binders which interact with the DNA in sequence-selective fashion. The rigorous benchmarking study to design new leads for DNA minor groove binders has also been mentioned in this book.