Structure based drug designing is an important endeavor in the field of structural bioinformatics. Previously the entire process was dependent on the wet-lab experiments to build libraries of ligand molecules. And the molecules used to be tested to determine their binding efficacies with protein target. However, the entire process is very lengthy and above all highly expensive. With the advent of supercomputers and increasing computational powers, the search process for finding suitable ligand molecules against target proteins have become more streamlined and cost-effective. Now the entire ligand search process is performed in-silico with the help of the techniques of virtual screening, molecular docking simulations and molecular dynamics studies. In the present chapter, a brief overview of the computational techniques involved in structure based drug designing is presented with a special emphasis on the thermodynamic principles behind the molecular interactions.