Identification of the bioactive conformation for mucin epitope peptides

Most of the drug molecules exhibit their biological activity through binding to the target protein. When the 3D structure of the binding site is unknown, pure ligand-based approaches are often used to perceive the 3D pharmacophore. However, dealing with conformational flexibility of ligands in such methods is still in the frontline of the current research. The special thermodynamic properties of the binding of flexible molecules, as derived here, show that the probability of the bioactive conformations in solution can determine the likelihood of binding. The binding activities can be obtained experimentally, while the probability of conformations in solution can be computed. Our present paper discusses the thermodynamic basis of performing 3D QSAR studies on molecules, with considerable conformational flexibility. In addition, we supply an algorithm to locate the bioactive conformations. The work is initiated to find the binding conformation of the therapeutically promising mucin epitope pentapeptides.