Albert Einstein College of Medicine inaugurated a Structural NMR Resource in 1995 with the hire of a new faculty member (Girvin), and the purchase of an initial four-channel Bruker DRX 600 MHz instrument (delivered late 1996) equipped for determining the structures and dynamics of biological macromolecules. This shared NMR Resource has been an enormous success. The PI has developed a program in the NMR structural analysis of membrane proteins, which has attracted collaborators from other institutions. Equal effort went into assisting other AECOM faculty incorporates NMR into their research programs. These efforts have been extremely productive, with many active, well-funded independent investigators including NMR-intensive Specific Aims in their current NIH and NSF grants. Due to these efforts, usage has grown to where instrument demand exceeds the capacity of our single 600 - by a factor of 2.5. We are requesting partial funding for a $1,026,900 Bruker DRX 600 MHz spectrometer with cryoprobe ($500,000 from the NIH, $200,000 from the NSF, with the remainder coming from school funds). This instrument will enable the participating group of independent investigators to accomplish the specific aims of their NIH and NSF funded proposals. The projects fall into four broad areas: i) membrane protein structure and function (Investigators Girvin, Spray, Almo, Krulwich, and Cramer), ii) protein folding and dynamics (Investigators Callender, Grubmeyer, and Girvin), iii) enzyme mechanism, regulation, and structure (Investigators Backer, Schramm, Blanchard, and Grubmeyer), and immunology (Investigators Nathenson and Almo).