- Research Overview
- Chemical Biology and Medicinal Chemistry
- Chemical Biology and Medicinal Chemistry Overview
- Discovering Enzyme Substrates and Functions
- Discovering Protein Ligands to Probe and Alter Function
- Discovering Enzyme Activators
- Analyzing Mechanisms of Drug Resistance via Chemical Biology
- Analyzing Enzyme Conformational Dynamics, Substrate Binding, and Catalysis
- Effective Drug Targeting of Pathogens via Medicinal Chemistry
- Computational Chemistry and Biology
- Computational Chemistry and Biology Overview
- Modeling protein regulation via allostery and post-translational modifications
- Visualizing and integrating bioinformatics and biomolecular data
- Modeling membrane permeation to optimize pharmacokinetics
- Determining enzyme function by predicting substrate specificity
- Physical Biology
- Protein and Cellular Engineering
- Protein and Cellular Engineering Overview
- Monitoring enzyme activity and disease biomarkers
- Generating human proteome antibodies via phage display and directed evolution
- Globally analyzing and dissecting apoptosis
- Proximity tagging of protein-protein interactions
- Investigating cellular interactions in tissues
- Creating fluorescent probes targeting the genome and key bio-pathways
- De novo design of catalytic and membrane proteins
- Probing and modulating membrane proteins
Chemical Biology and Medicinal Chemistry
Chemical biologists work at the interface of chemistry and biology to create and apply chemical tools and approaches to answer key questions about biological functions.
These chemical tools are used to inhibit or activate protein molecules, manipulating biological systems in order to understand them at increasing levels of detail. This approach also labels and quantifies molecules, tracking their activity.
Researchers probe, then decipher, the complex machinery of the proteome—the tens of thousands of different proteins that sequentially interact in a multitude of vital biological pathways.
Department scientists routinely focus on enzymes—proteins that selectively catalyze metabolic reactions. This work ranges from discovery of their functions and substrates to detailing of their mechanisms and kinetics.
Medicinal chemists seek to treat or prevent diseases by discovering and synthesizing small molecules that will selectively bind to target proteins and therapeutically alter their activity.
The department’s basic research validates these key molecular targets for intervention and develops leads for new or more effective medications.
But the discovery of potential targets (hits) is only the start of a highly iterative process by which drug leads are developed. Researchers follow up with rounds of screening, simulation, analysis, redesign, and more testing. The chemistry of the target molecule is modified in order to:
- Enhance affinity (reduce dosage).
- Increase selectivity (reduce off-target binding that causes side effects).
- Improve efficacy (including pharmacokinetic properties that allow it to reach its target in the body)
Department scientists apply rational drug design methods that are guided by detailed analyses of biological systems and target proteins. They focus on discovering and improving molecules such as analogs of known binders and enzyme substrates, or those with geometries and electrostatics that complement target binding sites.
These efforts are aided by the development of computational models of molecule docking as well as high-throughput screening—automated assays that allow the simultaneous testing of tens of thousands of potential effector molecules (ligands).
- Discovering enzyme substrates and functions
- Discovering protein ligands to probe and alter function
- Discovering enzyme activators
- Analyzing mechanisms of drug resistance via chemical biology
- Analyzing enzyme conformational dynamics, substrate binding, and catalysis
- Effective drug targeting of pathogens via medicinal chemistry
Faculty members engaged in this research area
- Steven Altschuler, PhD
- Michelle Arkin, PhD
- Charles S. Craik, PhD
- William DeGrado, PhD
- Sheng Ding, PhD
- Pamela England, PhD
- Danica Galonić Fujimori, PhD
- Zev Gartner, PhD
- Jason Gestwicki, PhD
- Stephen Kahl, PhD
- Michael Keiser, PhD
- Aashish Manglik, MD, PhD
- Susan Miller, PhD
- Paul Ortiz de Montellano, PhD
- Adam Renslo, PhD
- Ian Seiple, PhD
- Brian Shoichet, PhD
- Xiaokun Shu, PhD
- Lei Wang, PhD
- Jim Wells, PhD
- Lani Wu, PhD
- Balyn Zaro, PhD