2. Design of the inhibitor molecules

Pharmacophore modeling- This approach is more relevant when the 3-D structure or homology model of an enzyme is not known but the substrate or the ligand is known. A pharmacophore is a spatial arrangement of the functional group present on the ligand needed for the binding. To determine the pharmacophore, a series of ligand molecules are superimposed so that similar groups come together. The common functions are identified and categorized. The functional groups present in the ligand molecule are hydrogen bond acceptor, donor, aromatic ring system, hydrophobic and hydrophilic area etc (Figure 40.2). In the screening process, each molecule from the database is fitted into the pharmacophore model and the quality of agreement is assessed with a score. The program for pharmacophore modeling and screening are catalyst, galahad, MOE and Phase.

Figure 40.2: Pharmacophore with the different functional groups.