James Solomon Fraser
University of California-San Francisco, CA·Biophysics
Proteins and other large biological molecules are not frozen in one shape. They constantly flicker between several related shapes, called a conformational ensemble.
- Fields
Biophysics
Biochemistry
Pharmacology
- Topics
structural biology
conformational ensembles
protein dynamics
- Grants
- 1 known grant, through Aug 2027
What they work on
- Improve computational methods for finding and modeling alternative protein shapes in cryoEM density maps, extending the multiconformer modeling the group built for X-ray crystallography.
- Test on a large scale how ligand binding changes protein conformational heterogeneity, the range of shapes a protein adopts, using ensemble modeling of structural data.
- Develop better validation and comparison of ensemble model types, and quantify density signals for alternative conformations, hydrogens and chemical modifications.
- Determine the structural basis of new molecules that counter antibiotic resistance, and map the conformational landscape of the multi-subunit enzyme glutamine synthetase.
More about the research
Drugs and mutations often work by shifting the balance among these shapes. Yet most structural biology still describes each molecule with a single static structure. This research aims to model molecules as collections of shapes instead, and to use those models to design better drug-like molecules and to engineer proteins.
Why it matters
Modeling the many shapes a protein takes could help chemists design drugs that bind more precisely and help engineers design proteins with new functions. The project's planned work on molecules that counter antibiotic resistance points to one direct use. The open software and shared X-ray and cryoEM data could also help other structural biologists find hidden protein shapes.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Galina Lepesheva
Vanderbilt University, TN·Biochemistry
Determine how large-scale shape changes guide CYP51, the sterol-making enzyme targeted by antifungal drugs, through each step of its three-step reaction, using X-ray crystallography, cryo-electron microscopy and computational approaches.
Vukica Srajer
University of Chicago, IL·Biophysics
Install and test new hardware to generalize Electric-Field Stimulated X-ray crystallography, in which strong external electric fields induce motions in protein crystals that are then recorded by X-ray diffraction at atomic resolution.
Xiaojing Yang
University of Illinois Chicago, IL·Biophysics
Determine full-length cryo-EM structures of a bacteriophytochrome and a dual-sensor photoreceptor kinase in different signaling states by resolving structural heterogeneity, meaning the mix of shapes the proteins adopt.
The school
University of California-San Francisco: 89 labs on PI Pages, $2.1B a year on research, 164 research doctorates a year.
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