United Graduate School of Drug Discovery and Medical Information Sciences, Department of Gene and Development, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
Curr Top Med Chem. 2013;13(19):2432-40. doi: 10.2174/15680266113136660171.
A strategy of logical drug design (LDD) and its application to prion diseases are reviewed. LDD is primarily based on the localizability of a hot spot which initiates structural instability in the target protein. It is also based on the regulability of the hot spot by small compounds, their designabilty by a computer, their organic synthesizability and the specificity of their functions once administered to the biological organisms. Unification of localizability, regulability, producibility and specificity is the central theme of LDD. Theoretical foundation of LDD based on quantum theories is initially outlined. The localizability using nuclear magnetic resonance (NMR), the regulability by a medical chaperone, the synthesizability, and the functional specificity accomplished thus far, are then described.
本文综述了逻辑药物设计（LDD）策略及其在朊病毒疾病中的应用。LDD 主要基于热点的局部性，该热点在靶蛋白中引发结构不稳定性。它还基于热点可被小分子调节、小分子可通过计算机设计、可有机合成以及一旦施用于生物机体时功能的特异性。局部性、可调节性、可生产性和特异性的统一是 LDD 的核心主题。基于量子理论的 LDD 的理论基础最初被概述。然后描述了使用核磁共振（NMR）的局部性、医学伴侣的调节性、合成性和迄今为止实现的功能特异性。
