Demonstrating Rational Drug Design Using Free Docking Software

Students in the biochemistry and physical chemistry laboratories computationally modeled the docking of the HIV protease inhibitor Indinavir, a current therapeutic marketed by Merck. Students then hypothesized how to improve upon this inhibitor by searching for new interactions between the drug and HIV protease. Once their new, rationally designed inhibitor was built, its binding to HIV protease was modeled. The changes were evaluated through comparisons of calculated binding energies. This laboratory exercise offers an excellent approach, for either biochemistry or computational chemistry courses, to expose students to the role computers play in the pharmaceutical industry toward the design of new therapeutic agents. This simulation generates student interest through visual analysis of the interactions formed between the drug and enzyme, while showcasing the challenges associated with rational drug design. The experiment utilizes free software that can run on any Microsoft Windows operating system.