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Gentle, fast and effective crystal soaking by acoustic dispensing
Patrick M Collins1, Jia Tsing Ng2, Romain Talon2
1Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, England.
Acta Crystallographica. Section D, Structural Biology
|March 15, 2017
Summary
Acoustic droplet ejection enables high-throughput, gentle soaking of protein crystals with small molecules. This method accelerates drug discovery by improving X-ray diffraction reproducibility and solvent tolerance.
Area of Science:
- Structural Biology
- Biochemistry
- Drug Discovery
Background:
- Modern beamlines facilitate high-throughput data collection, but sample preparation remains a bottleneck.
- Traditional crystal soaking methods require gentle, stepwise concentration increases, limiting throughput.
Purpose of the Study:
- To introduce acoustic droplet ejection as a novel method for protein crystal soaking.
- To demonstrate its efficiency, gentleness, and impact on X-ray diffraction quality.
Main Methods:
- Utilizing acoustic droplet ejection for precise, low-volume dispensing of small molecules onto protein crystals.
- Optimizing soaking regimens for enhanced solvent diffusion and crystal tolerance.
Main Results:
- 1000 unique soaks completed in under 10 minutes with minimal compound consumption (nanoliters).
- Improved X-ray diffraction reproducibility and increased solvent tolerance of protein crystals.
- Successful application demonstrated with the JMJD2D protein target.
Conclusions:
- Acoustic droplet ejection significantly enhances throughput and reproducibility in protein crystal soaking.
- This technique accelerates structure-based drug design by enabling efficient screening of small molecules.
