Determination and uses of the atomic structures of ribosomes and ribosomal subunits and their ligand complexes

A method of growing a crystal of a ribosome or a ribosomal subunit comprising:

• (a) isolating a ribosome or a ribosomal subunit;
• (b) precipitating the ribosome or ribosomal subunit;
• (c) back-extracting the precipitated ribosome or ribosomal subunit to obtain a solution;
• (d) seeding the back-extracted solution;
• (e) growing a crystal of the ribosome or ribosomal subunit from the seeded solution by vapor diffusion at room temperature;
• and
• (f) harvesting the crystal.

A method of obtaining X-ray diffraction data for a crystal of a ribosome or a ribosomal subunit comprising:

• (a) obtaining a crystal of a ribosome or a ribosomal subunit, wherein the crystal has one or more of the following characteristics:
• (1) an average thickness of greater than 15 μm;
• (2) untwinned;
• and
• (b) using X-ray crystallography to obtain X-ray diffraction data for the crystal of the ribosome or ribosomal subunit.

A method of obtaining X-ray diffraction data for a complex of a ribosome and a ligand or a complex of a ribosomal subunit and a ligand comprising:

• (a) obtaining a crystal of a ribosome or a ribosomal subunit, wherein the crystal has one or more of the following characteristics:
• (1) an average thickness of greater than 15 lm;
• (2) untwinned;
• (b) diffusing a ligand through the crystal and permitting the ligand to attach to the crystal so as to form a complex;
• and
• (c) using X-ray crystallography to obtain X-ray diffraction data for the complex.

A method of obtaining X-ray diffraction data for a complex of a ribosome and a ligand or for a ribosomal subunit and a ligand comprising:

• (a) obtaining a co-crystal for a complex of a ribosome and a ligand or for a complex of a ribosomal subunit and a ligand, wherein the co-crystal has one or more of the following characteristics:
• (1) an average thickness of greater than 15 μm;
• (2) untwinned;
• and
• (b) using X-ray crystallography to obtain X-ray diffraction data for the complex.

A method of obtaining a modified agent comprising:

• (a) obtaining a crystal of a ribosome or of a ribosomal subunit;
• (b) obtaining the atomic coordinates of the crystal;
• (c) using the atomic coordinates and one or more molecular modeling techniques to determine how to modify the interaction of an agent with a ribosome or ribosomal subunit;
• and
• (d) modifying the agent based on the determinations obtained in step (c) to produce a modified agent.