Author(s) :

Hailey Haein Yoon.

Volume/Issue :

Abstract :

Small-molecule drugs, organic compounds that interact with proteins and enzymes, represent a powerful approach for treating genetic diseases. These drugs are designed to alter specific molecular disease targets and do so with reduced off-target effects. Furthermore, these drugs offer ease in consumption through oral delivery. New technology, especially computational tools, have enabled the enhanced modeling of design of small-molecule drugs. These advancements are particularly effective in the treatment of genetic disease, where targeting mutated proteins can restore function and reduce disease progression. This project uses SwissDock molecular docking to assess how modifying chemical structures of the cystic fibrosis small-molecular drug Ivacaftor can enhance the drug’s interaction with the mutated CFTR protein. Among the 4 modified Ivacaftor analogs tested alongside the unmodulated structure, hydroxyl-group-deleted Ivacaftor was shown to have the lowest average SwissParam score and thus the highest binding affinity to the mutated CFTR protein. The broader implications of this work highlight how structure-based drug design can lead to the development of more effective treatments for genetic disease and be applied for the treatment of other conditions, ultimately expanding the scope of precision medicine.