Skarzynski Tadeusz, Thorpe James
GlaxoSmithKline, UK.
Acta Crystallogr D Biol Crystallogr. 2006 Jan;62(Pt 1):102-7. doi: 10.1107/S0907444905034281. Epub 2005 Dec 14.
Protein crystallography methods applied by research teams in the pharmaceutical industry to support the process of discovery of new medicines are not greatly different from those used by academic structural biology groups. However, owing to the specific aims of the pharmaceutical industry, the approaches and working practices are often quite distinct. This applies to both the determination of novel structures of drug targets and complexes of these targets with potential drugs. To make any significant impact on ongoing medicinal chemistry projects, crystal structures have to be delivered on time and must provide answers to specific questions. Owing to the high number of crystal structures typically solved by industrial research groups, development of technology and computational methods which speed up the process and increase throughput is of vital importance. This paper presents an overview of current approaches to X-ray data collection and processing within the industrial environment, with examples of how technology is used to address the challenges structural biology faces in this "high-throughput-everything" period.
制药行业的研究团队用于支持新药发现过程的蛋白质晶体学方法,与学术结构生物学团队所使用的方法并无太大差异。然而,由于制药行业的特定目标,其方法和工作实践往往大不相同。这适用于药物靶点新结构的测定以及这些靶点与潜在药物的复合物的测定。为了对正在进行的药物化学项目产生任何重大影响,晶体结构必须按时交付,并且必须回答特定问题。由于工业研究团队通常解析的晶体结构数量众多,因此开发能够加速这一过程并提高通量的技术和计算方法至关重要。本文概述了工业环境中当前的X射线数据收集和处理方法,并举例说明了如何利用技术应对结构生物学在这个“一切高通量”时期所面临的挑战。