Finding the Right Fit in Drug Discovery
After completing a Biological Chemistry Specialist at UTM, Zuhair Ahmed joined the labs of Scott Prosser and Amanda Hargrove in 2023 to pursue a PhD in Chemical Biology, Medicinal Chemistry, and Biophysical Chemistry. With the support of the CPS Teaching Fellowship, Zuhair introduced computational screening into the 3rd-year Techniques in Biological Chemistry I course – often the first exposure undergraduates have to modern methods in drug discovery. Here, students complete a docking module to computationally simulate drug-target interactions – a key first step in most discovery pipelines. However, unlike industrial pipelines that screen millions of compounds, software limitations restrict the module’s scope to just a handful of drugs. Thus, Zuhair wanted to introduce students to 1) screening libraries of drugs computationally, 2) identifying top performers, and 3) suggesting routes for improving them.
To investigate which chemical groups on a molecule contribute to target engagement, students use an open-source program called AutoDock Vina to simulate binding and evaluate therapeutic potential. However, the software’s manual operation through command prompt limits throughput, requiring individual commands for each ligand-target pair. To streamline the process, Zuhair introduced PaDEL-ADV – an open-source application with a user-friendly interface that automates Vina, enabling high-throughput docking and ranking of compound libraries. The integration of PaDEL-ADV at no additional cost shifted the students’ focus to understanding patterns and key chemical motifs that make a potent therapeutic tailored to their target. Together with the course instructor, Qirat Ashraf, he also modified assessments to prompt students to propose novel compounds and consider target flexibility.
As docking is an essential first step in drug discovery, experience with these computational tools is vital in medicinal chemistry. As part of Zuhair’s pedagogic project, students are encouraged to engage in analytical thinking that will prepare them for both academic and industrial careers in pharmaceutical development.
