Computer-Aided Drug Design for the Organic Chemistry Laboratory Using Accessible Molecular Modeling Tools

摘要

Drug design and development is a central thrust of current research. Thus, it is imperative that students pursuing degrees in a variety of chemical and biological fields become exposed to the research and development process early in their curriculum. The organic chemistry laboratory course, required for many prehealth professional degree programs in biology and related fields, is well-suited for a first introduction to processes critical to the development of pharmaceuticals. While all of the components of research and development would encompass a multitude of coursework, focusing on aspects of ligand design, an important aspect of drug research and development, led by molecular modeling (computer-aided drug design), is ideal for a multiweek project during the second semester organic laboratory course. By using free, accessible online software like PatchDock, Chimera, and SwissADME, students are led through a manageable drug design project focused on generating noncovalent inhibitors of acetylcholinesterase (AChE) derived from known therapeutics. Not only do students dock their own unique inhibitors, but also they are led through gathering important toxicological data points through modeling with SwissADME. Overall, students are given the opportunity to see features of the drug design process beyond the synthesis of complex organic molecules within a research-like environment.