High-throughput X-ray protein crystallography offers unprecedented facilitation to structure based drug discovery. The popular way to prepare crystals of target protein in complex with a candidate compound is the soaking method. However, the method often causes damage due to osmotic pressure to crystals, especially when a compound is dissolved in an organic solvent or solution with high ionic strength. These solutions damage protein crystals by osmotic shock. To overcome this difficulty, we have developed a novel technique to grow protein crystals in the concentrated hydrogel. Here, we demonstrate that protein crystals grown in hydrogel are stable to soaking and suffer less damage.
