Abstract
A preliminary molecular structure for a system, which may or may not be known, is the first step in a typical investigation using ab initio techniques. A stable system is generated by a geometry search using an energy minimization method (usually a local minimum or transition state). Subsequently, it is easy to obtain any energetic properties (such as atomization energies, formation temperatures, binding energies) or expectation values or quantifiable quantities from the wave function of the molecular system and its fragments. The stability of such a system can be determined by considering the second derivative of the energy with respect to the spatial coordinates (also known as the Hessian matrix). It could be a goal to find out how the system interacts with other systems and eventually to decipher the synthesis pathways. Therefore, this chapter presents a recent application of approaches based on density functional theory (DFT) to study chemical processes at the catalytic sites of enzymes. The focus is on the interaction of small organic molecules with the ability to inhibit a catalytic cysteine of the malaria parasite, in the area of drug design.