藥物設計(英語:Drug design),常稱理性藥物設計(Rational drug design),是根據生物靶點(Biological target)的現有知識尋找與發現新型藥物的過程[1]。最常見的藥物類型如有機小分子藥物,可激活或抑制蛋白質等生物分子功能,進而為患者在治療中獲益。藥物設計可狹義地定義為藥物分子設計,這些藥物分子的形狀和原子所帶電荷與生物分子靶標存在互補關係,即「鎖鑰模型」(Lock and key model),因此藥物分子會與生物靶標存在結合力。使用電腦分子建構技術進行藥物設計可稱為計算機輔助藥物設計(Computer-aided drug design,CADD)。根據對於生物目標的化學結構來進行設計,稱為結構藥物設計(Structure-based drug design)[2]。除了小分子之外,現今包括多肽與單克隆抗體治療在內的眾多生物治療方式,在製藥領域變得越發重要。與此同時,各種提高藥物親和力、選擇性和穩定性的算法在基於蛋白質治療的領域中也持續發展[3]。
基於配體的藥物設計(或間接藥物設計)基於與已知生物靶標與確定分子結合的數據。這些分子可用於推測藥效團模型,即分子中可結合靶標中最小且必要的結構片段[32]。同樣的,構建生物靶標模型可基於與其結合的分子,同時該建模反之可用於設計與靶標相互作用的新化學實體(New chemical entity,NCE)。又或者,該建模還可歸納量化結構-活性關係(QSAR),即通過計算分子性質與實驗測定的生物活性之間的關聯度。這些QSAR關係還可繼續通過計算機模擬迭代,以預測新的候選類似物的生物活性[33]。
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