Advantages of X-ray Crystallography in Drug Discovery Research

Abstract

The paradigm shift in drug discovery that began in the early 1990s was the development of Structure Based Drug Design（SBDD）as a means of rational drug design for disease targets. The greatest advantage of X-ray analysis is that once the crystal structure is obtained, structural information can be fed back very quickly under almost the same conditions for soaking and co-crystallization, contributing to lead optimization in the early stages of drug discovery. In addition, it is unique in that it covers target molecules from small molecular weights（20-30 kDa）to large molecular weights（100 kDa～）. On the other hand, it has many weak points such as dynamic structure close to the physiological state, identification of hydrogen atoms, and acquisition of charge information, which, when combined with multiple methods in a complementary manner, will contribute to a significant reduction in the lead optimization period in the future.