The SGPP consortium will determine and analyze the three-dimensional structures of a large number of proteins from major global pathogenic protozoa, Leishmania major, Trypanosoma brucei, Trypanosoma cruzi and Plasmodium falciparum. These organisms are responsible for the debilitating, and often lethal, diseases: leishmaniasis, sleeping sickness, Chagas' disease and malaria. The unique biological characteristics of these organisms coupled with the medical relevance makes them attractive sources of proteins for high-throughput structure determination. In addition, active genome sequencing projects are underway for all four organisms. The SGPP consortium will develop and explore several new technologies for high-throughput protein expression and structure determination in the course of this pilot project.

1. Using protein structure prediction methods and medical relevance in target selection;
2. Rapid evaluation of expression levels and solubility of thousands of variants of proteins obtained by scrambled sequences from different Leishmania strains;
3. Using two-hybrid methods to discover and solve structures of soluble heteromultimers;
4. Significant emphasis on membrane proteins with discovery, by two-hybrid methods and Fv phage libraries, of interacting soluble partner proteins to be used for co-crystallization and MAD phasing;
5. Intensive use of robotics in the crystallization, crystal mounting, data collection steps;
6. Development of bromine-containing co-crystallant libraries;
7. Exploring the power of crystal annealing in improving mosaicity and resolution;
8. Using predicted protein structures in electron density interpretation;
9. Using ligand docking procedures, deep sequence family alignments and very weak structural homologies to derive function from structure.