Precipitant Synergy™ uses synergistic combinations of mechanistically distinct precipitating agents to obtain crystallization hits from a starter set of 64 different formulations.

Each Precipitant Synergy™ (PS) formulation contains a carefully selected combination of at least two mechanistically distinct precipitating agents including:
(i) salts that affect the activity coefficient of water at high concentration;
(ii) organic solvents which alter the dielectric constant of the solvating medium
(iii) and PEGs which operate by increasing molecular crowding.

Tests with 10 different proteins showed that the Precipitant Synergy™ screen roughly triples the number of different crystals obtained compared to other screens [Majeed, S., Ofek, G., Belachew, A., Huang, C.-C., Zhou, T., Kwong, P.D. (2003) Structure, 11: 1-20]. Patent Pending. Each of the 64 formulations in the Primary PS screen are prepared with precipitants at a fairly high concentration, close to their maximum solubility, in order to reach or exceed the protein’s precipitation point. The 64 PS formulations also encompass a broad pH range from 5.5 to 8.5, with a diverse array of eight different buffering agents. Rapid optimization of initial hits (precipitation and/or crystallization) is achieved by either serial dilution of the lead Primary PS formulation, or by re-screening with Expanded PS formulations that contain precipitating agents at 67% or 33% of their Primary concentration, while holding the buffer and additive compositions constant. Hence, the 192-formulaion Expanded format has three sets of the 64 PS formulations with precipitant concentrations at 100% (Primary 64), 67%, or 33%. The buffer/additive matched PS formulations can also be serially mixed to arrive at very fine grid expansion series from 100% to 33% concentrations of the Primary level precipitants. Use of the Expanded 192 PS formulation kit allows researchers to rapidly deploy an internally consistent approach for the optimization of protein crystal growth.