Funds are requested for the acquisition of a Malvern MicroCal PEAQ-ITC (Isothermal Titration Calorimeter). ITC data will allow characterizing the thermodynamic signatures of a number of proteins that bind diverse targets and mediate fundamental functions, from immune responses and synapses to virology. Therefore, this equipment will significantly enhance our understanding of the nuanced relationships between thermodynamics, structure, and function, and expedite development and design of more potent and specific drugs for a wide variety of diseases including microbial infections, autism, and schizophrenia. Our previous, now defunct, VP-ITC was extensively used (by over a dozen research groups) and provided not only fundamental knowledge, but was valuable in securing many investigator-initiated federal grants. We cannot overemphasize the importance of an ITC for the Sealy Center for Structural Biology and Molecular Biophysics (SCSB) core faculty and our other colleagues who are interested in the molecular mechanisms of their proteins of interest. The new instrument will be housed in the existing SCSB space at UTMB, and will be supported by the SCSB. A Ph.D.-level solution biophysics Facility Manager, also fully supported by the SCSB, will oversee the system. Scheduling of the instrument will be web-based, and any conflicts will be resolved through a steering committee. Approximately 10% of the available hours will be reserved for new and outside users, as well as for pilot studies, and in particular, priority will be given to new faculty investigators to facilitate their competition for NIH support. Further, we are confident that the new ITC will stimulate new collaborations among investigators in our University.
Knowledge of the thermodynamics that drive macromolecular interactions is essential for understanding the nuanced relationship between thermodynamics, structure, and function. Funds are requested for purchase of a Malvern MicroCal PEAQ Isothermal Titration Calorimeter that will allow us to characterize proteins that bind diverse targets and mediate fundamental roles in human health and disease, and expedite development and design of potent drugs for a wide variety of diseases including neurological disorders and microbial infections.
|Sepuru, Krishna Mohan; Nagarajan, Balaji; Desai, Umesh R et al. (2018) Structural basis, stoichiometry, and thermodynamics of binding of the chemokines KC and MIP2 to the glycosaminoglycan heparin. J Biol Chem 293:17817-17828|