Macromolecular Structure & Interactions
We support structural studies and studies of macromolecular interactions aimed at understanding mechanisms of cancer-related biomolecules, including signaling proteins, chaperones, enzymes involved in DNA repair, etc. and to utilize knowledge of structures and interactions, together with the ability to perform screening and investigate small molecule binding, to develop and discover novel therapies for treating cancer.
- Automated preparation of NMR samples, including addition of compounds from the Maybridge Ro3 fragment library, using the Gilson 213 liquid handler
- Acquisition of NMR data, including automated acquisition, with hundreds of NMR samples
- Assistance with NMR data processing, analysis and three dimensional structure determination
- Assistance with titrations of isotope labeled macromolecules with unlabeled binding partners to map interaction surfaces with other macromolecules, ligands and small molecule therapeutics
- Automated setup and imaging of vapor diffusion or microbatch crystallizations trials
- Automated addition of compounds from the Maybridge Ro3 fragment library to already formed crystals
- Acquisition of X-ray diffraction data, including fragment screens, with hundreds of crystals
- Assistance with X-ray data processing, macromolecular model building and structure refinement
- Analysis of the kinetics and thermodynamics of interactions, including protein:protein, protein:nucleic acid, or protein or nucleic acid:inhibitor screening utilizing SPR with either our BIAcore 3000, which is suitable for studying macromolecular interactions, or our recently acquired BIAcore T100 instrument, which has greater sensitivity and is suitable for studying macromolecular or small molecule interactions.
- Analysis of the thermodynamics of self-associating systems, simultaneous characterization of molecular weight distributions and degree of globularity, and study of conformational changes and macromolecular interactions utilizing one of our three Beckman-Coulter XL series analytical ultracentrifuges, two of which are equipped with absorbance and interference optical systems, and one equipped with absorbance and fluorescence optical systems.
- Analysis of diffusion coefficients, monodispersity, particle size distributions, stoichiometries, molecular weights and assembly/disassembly rates using our Wyatt Dyno Nanostar DLS/SLS instrument.
- Analysis of binding affinities, enthalpies and stoichiometry for protein:protein, protein:nucleic acid, or protein or nucleic acid:small molecule binding using our MicroCal VP-ITC instrument.
Andrew Hinck, Ph.D., director
Eileen Lafer, Ph.D., co-director
John Hart, Ph.D., co-director