Drug Discovery and Development Laboratory
​藥物設計開發實驗室

The grand future of biotechnology will be centered on precision medicine as the main direction for personal healthcare. Drug development, including small molecule compounds and protein-based drugs, is the foundation and essence of medical drug therapy, and it is also a major industry within biotechnology. Our laboratory is a research lab that integrates biochemistry, molecular biology, and structural biology, with the primary research objective being "new drug development."

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Our research focuses on disease-related proteins as the main targets, combining biophysical and biochemical techniques, molecular biology experiments, structural biology experiments, and cellular experiments to screen, design, validate, and confirm the efficacy of potential small molecule and protein-based drugs.

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The application of structural biology includes structure-based drug screening, such as molecular docking and pharmacophore-based inhibitor screening. Additionally, it involves ligand-based pharmacophore identification for drug screening applications based on the structure of small molecules. These biomimetic systems can be used to screen for potential small molecule inhibitors. Furthermore, natural product and traditional Chinese medicine small molecule databases will be utilized in drug development, aiming to develop natural health products and therapies with low side effects and no toxicity for humans.

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The small molecules identified through structure-aided drug design will be experimentally confirmed for their inhibitory effects. Biochemical experiments will be used to determine the inhibitory capabilities of the small molecule inhibitors. Subsequently, we will explore the binding affinity, binding specificity, and mode of action between the small molecule inhibitors and the target proteins. Techniques such as isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), and biolayer interferometry (BLI) will be employed. Additionally, nuclear magnetic resonance (NMR) and protein crystallography (X-ray) will be used to analyze the molecular interactions between small molecule inhibitors and target proteins, providing crucial information for subsequent chemical synthesis and modification of small molecule structures to optimize their efficacy.

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The next crucial step is the confirmation of the inhibitors' efficacy by validating their bioactivity and therapeutic effects at the cellular and animal levels. Drug efficacy tests will be conducted through cell and animal experiments. Finally, the research findings will be published in international journals and protected by patents.

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Our laboratory is interdisciplinary, with strong collaborations and interactions with various research institutes such as Academia Sinica and the National Research Institute of Chinese Medicine. We welcome students from diverse backgrounds, including chemistry, physics, biochemistry, molecular biology, medicine, life sciences, and bioinformatics, to join us.

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生物科技大未來，將是一個以精準醫學作為個人醫療上的主軸方向。其中，藥物開發 (例如，小分子化合物以及蛋白質藥物) 是醫學藥物治療的基礎與精隨，更也是生物科技的一大產業。本實驗室研究室是一個整合生物化學，分子生物學以及結構生物學的研究室，主要研究目的為"新藥開發"。

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實驗室研究方向以疾病相關的蛋白質為主要標靶，結合生物化學技術 (Biophysical and Biochemical techniques)， 分生實驗，結構生物學實驗，細胞實驗，來篩選，設計，驗證，確效有潛力的小分子藥物與蛋白質藥物。

結構生物學之運用、包含以標靶蛋白結構為基礎的藥物篩選 (Structure-Based Drug Screening)，例如分子對接　(Molecular Docking) 與藥效基團抑制劑篩選 ( Pharmacophore-Based Inhibitor Screening) 。 另外也包含以小分子的結構為基礎，建立藥效基團 (Ligand-Based Pharmacophore Identification) 用以藥物篩選應用。這些仿生物系統將可以用來篩選有潛力的小分子抑制劑。此外，天然藥物以及中草藥小分子資料庫將用在藥物開發上，目的是開發對人體副作用低且無毒性的天然物保健食品與治療方式。

由結構生物學輔助的藥物設計所篩出的小分子、會以實驗的方式確認其抑制效果。生物化學的實驗將用來確定小分子抑制劑的抑制能力。接著探討小分子抑制劑與標靶蛋白質之間的結合親合性 (Binding Affinity)， 專一性 (Binding Specificity)，以及交互作用的機制 (Mode of action)。這類的技術有等溫滴定熱分析 (ITC)，表面等離子共振 (SPR) 與生物膜層光學干涉技術 (BLI) 。此外，核磁共振技術 (NMR)， 蛋白質晶體結構技術 (X-ray) 將用來解析小分子抑制劑與標靶蛋白之間的分子交互作用；提供後續在化學合成修改小分子結構重要的訊息，來最佳化小分子抑制劑的功效。 

接著最重要是抑制劑確效的部分，驗證其在細胞層面與動物體內的生物活性與疾病治療效果。利用細胞試驗與動物實驗來做藥效測試。最後也會將所得到的研究成果發表於國際期刊並以專利保護。

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本實驗室屬跨領域研究與許多研究單位如中央研究院、國家中醫藥研究所、有良好的合作與互動。歡迎化學、物理、生化、分子生物、醫學、生科、生物資訊等等不同背景學生加入。