Novel buffer systems for macromolecular crystallization

In protein crystallization, screening is initially performed to obtain an indication of the conditions under which a macromolecule might crystallize. These preliminary conditions are then optimized to produce (in a perfect world) well diffracting crystals; this process of optimization often involves fine grid screening around the initial conditions. An issue in optimization is to find factors which are independent, so as to simplify the analysis of the results of optimization trials. This is necessarily difficult with buffers, as a buffer and its pH range tend to be very highly correlated. Multi-buffer systems for pH modulation are presented which enable a broad pH range to be sampled without changing the chemical composition of the buffering component.