Ethan A Merritt

Research Associate Professor
Departments of Biochemistry and Biological Structure
Biomolecular Structure Center

Methods development in protein crystallography
I am broadly interested in developing and applying new technologies and new computational techniques to problems of molecular structure. I have worked on beamline design, robotics, and the creation of new and better computational tools for modelling, analyzing, visualizing and interpreting protein structures. One ongoing project is the use of TLS models to detect and describe local flexibility in proteins. These models are applicable to protein-protein docking and to model ligand binding at a flexible binding site.

Structural genomics
My lab is one of several UW groups interested in using structural genomics to identify opportunities for drug design targetting parasitic diseases. The MSGPP (Medical Structural Genomics of Pathogenic Protozoa) Consotium has successfully identified and characterized several promising target proteins from these disease organisms.

Structure-based drug design
One current project is the development of drugs targetting Ca-dependent Protein Kinases (CDPKs), a class of proteins found in apicomplexan parasites but not in humans. We have identified very promising nanomolar CDPK inhibitors that are active against Cryptosporidia and Toxoplasma. Further work may capitalize on the presence of homologous target proteins in the malarial parasite (Plasmodia) and in the related protozoan pest Eimeria. This work is a collaboration with UW groups in the departments of Chemistry, Global Health, and Medicine.

Links to further information on these research projects

MSGPP structural genomics project
Synchrotron radiation, X-ray anomalous scattering and MAD phasing
Bacterial Toxins (past project)
Raster3D photorealistic molecular graphics
Refinement, analysis, and validation of atomic resolution protein structures
TLSMD inference of protein dynamics from single crystal structures

Representative Publications