Although no single drug has been designed solely by computer techniques, the contribution of these methods to drug discovery is no longer a matter of dispute. All the world’s major pharmaceutical and biotechnology companies use computational design tools. At their lowest level the contributions represent the replacement of crude mechanical models by displays of structure which are a much more accurate reflection of molecular reality, capable of demonstrating motion and solvent effects. Beyond this, theoretical calculations permit the computation of binding free energies and other relevant molecular properties. The theoretical tools include empirical molecular mechanics, quantum mechanics and, more recently, statistical mechanics.This paper is concerned with the modeling of a new drug for heart disorders making 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA reductase) as a target and Atorvastatin, as the drug used. This drug is modified structurally and its derivatives obtained as such are tested for their affinities in binding with the protein. Objectives of this paper are to optimize the structures of the drug derivatives, to calculate the energies of the optimized derivated structures and optimized protein-ligand structures, to dock the ligands (derivatives) with the protein structure and calculate the binding affinities of each molecule, to compare the binding energies and identify the best lead compound with maximum stability.