Single Molecule Imaging Techniques to Aid Crystallization

Crystallization of biomolecules is widely used in academia as well as industry to determine the structure of biomolecules. It's important to know the structure, because reactions between molecules is driven by their shape - different things happen when a given biomolecule is one conformation or another. These structure are used to understand the functions of the biomolecule, as well to do in silico (computer-based) drug discovery. However, it is difficult to find the right conditions (buffer, temperature, etc) under which a biomolecule will form a crystal -- testing each proposed set of conditions is time-consuming and expensive, as it requires time on an x-ray beamline. It is even harder and more time-consuming to identify conditions under which a biomolecule will crystallize in one desired conformation out of many possible ones.

This invention uses smFRET to rapidly determine optimal crystallization conditions for a biomolecule in a desired conformation. smFRET is a microscopy technique that allows investigators to study conformational dynamics of biomolecules in real time. Changing conditions between smFRET sessions allows simple, rapid determination of optimal conditions to hold a biomolecule in a given conformation.

This method is applicable to many types of biomolecules, including proteins, peptides, proteoliposomes, nucleic acids, oligonucleotides, and/or complexes of the any of the foregoing.

Potential Applications

• Crystallization optimization services
• Drug screening