Kempkes Robin, Stofko Elizabeth, Lam Kam, Snell Edward H
Hauptman-Woodward Medical Research Institute, 700 Ellicott Street, Buffalo, NY 14203, USA.
Acta Crystallogr D Biol Crystallogr. 2008 Mar;64(Pt 3):287-301. doi: 10.1107/S0907444907067613. Epub 2008 Feb 20.
The Hauptman-Woodward Medical Research Institute runs a high-throughput crystallization screening service in which macromolecules are screened against 1536 potential crystallization cocktails. Typically, multiple crystallization leads are identified. With a limited amount of sample, the question becomes ;How many leads can be optimized and which leads are most likely to produce X-ray diffraction data?'. In order to prioritize the hits for optimization, the amount of glycerol required to successfully cryocool each cocktail has been determined for the cocktails used in the high-throughput screen. Those hit conditions that require the minimum amount of cryoprotectant for successful vitrification will be closer in chemical make-up to the mother liquor. Hence, if the physical properties of the crystals are similar, one could logically prioritize leads that are more likely to produce diffraction based upon the chemical similarity of the native to the cryopreserved mother liquor.
豪普特曼-伍德沃德医学研究所提供一项高通量结晶筛选服务，在此服务中，会针对1536种潜在的结晶混合液对大分子进行筛选。通常会鉴定出多个结晶先导物。由于样品量有限，问题就变成了“可以优化多少个先导物，哪些先导物最有可能产生X射线衍射数据？”。为了对用于优化的命中物进行优先级排序，已针对高通量筛选中使用的混合液确定了成功冷冻冷却每种混合液所需的甘油量。那些成功玻璃化所需冷冻保护剂最少的命中条件在化学组成上会更接近母液。因此，如果晶体的物理性质相似，那么基于天然母液与冷冻保存母液的化学相似性，就可以合理地对更有可能产生衍射的先导物进行优先级排序。
