The Summer Science Program in Biochemistry
A brief introduction to how small molecules bond to enzymes and other proteins. Participants of the Summer Science Program in Biochemistry model an enzyme from a fungal pathogen and design a molecule to protect crops.
Fungal Inhibitor Design
All life processes are driven by enzyme-catalyzed reactions, and all enzymes are linear chains of amino acids whose sequence arises from DNA. Understanding how a limited set of 20 building blocks can give rise to extraordinary 3-dimensional structural and chemical diversity is one of the “holy grails” of biochemistry. This problem is of great practical importance, because most drugs are enzyme inhibitors, whether for medical or agricultural applications. Hunger is one of the biggest threats to human health, and new chemicals are constantly needed to safely and effectively combat pathogens that infect crops worldwide.
Participants will learn the fundamentals of enzyme structure, function, and evolution. Each team of three will combine bench experiments and computer tools to characterize a member of an enzyme family that is implicated in crop infection by fungal pathogens – one which has never been modeled by anyone before. They will submit their enzyme model to a database available to other scientists. Then, they will design a molecule that might safely protect crops from that specific fungus, by binding to the enzyme and inhibiting its activity.
The project goes beyond what is asked of undergraduates in an analytical biochemistry lab course. It demands hypothesis-building based on integration of existing information, critical analysis and interpretation of novel experimental results, and application of the novel information to portions of the drug design pipeline. These highly practical aspects of modern biochemical research will train students how to intellectually approach a biochemical research problem. Topics covered include:
- Biochemistry: affinity chromatography, gel electrophoresis, enzyme assays, kinetics, and inhibition, drug screening
- Molecular Modeling: homology modeling, ligand docking, molecular dynamics simulations, inhibitor optimization
- Mathematics: rate equations, linear and non-linear curve fitting, biostatistics
- Bioinformatics: Sequence similarity searching, multiple sequence alignment, secondary structure and binding motif prediction