課程資訊
課程名稱
分子辨識
Molecular Recognition 
開課學期
108-1 
授課對象
生物資源暨農學院  農業化學系  
授課教師
徐駿森 
課號
AC5066 
課程識別碼
623 U4340 
班次
 
學分
2.0 
全/半年
半年 
必/選修
選修 
上課時間
星期三8,9(15:30~17:20) 
上課地點
農化一第五 
備註
總人數上限:20人 
Ceiba 課程網頁
http://ceiba.ntu.edu.tw/1081AC5066_MR 
課程簡介影片
 
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課程概述

分子辨識課程是應用結構生物、化學生物與分子生物學來探討生命科學的一門課。無論在動物、植物或是微生物的系統,生命現象從微觀的角度來看就是細胞內生物分子經由交互作用而造成訊息傳遞與命令執行之功能。此外,醫學或農業上的病毒或病菌感染、也是藉由特定分子的辨識為起始,進而入侵宿主。瞭解這些生物分子之分子辨識作用,除了能說明其作用機制,並在應用上可發展策略用於抑制或促進其辨識作用及生物活性。  

課程目標
此課程以深入淺出的方式,一開始說明分子辨識的化學原理,接著介紹各項研究分子交互作用之結構與生物物理工具。並以數個具有啟發性的生物交互作用系統為範例。最後由文獻討論來讓參與課程者能將分子結構觀念帶入本身正在研究或有興趣的領域。  
課程要求
歡迎大三以上與研究所不同背景學生,但若未修過生物化學,請先與老師溝通。 
預期每週課後學習時數
 
Office Hours
每週三 13:00~15:00 
參考書目
Arthur M. Lesk, (2004). Introduction of Protein Science. Oxford University Press.
Gordon C.K. Roberts, (2000). NMR of Macromolecules-A practical approach, Oxford University Press.
Gale Rhodes, (2000). Crystallography Made Crystal Clear, Academic Press
 
指定閱讀
 
評量方式
(僅供參考)
 
No.
項目
百分比
說明
1. 
期中考 
20% 
 
2. 
期末考 
30% 
 
3. 
作業 
20% 
 
4. 
報告 
30% 
 
 
課程進度
週次
日期
單元主題
第1週
9/11  Introduction 
第2週
9/18  NSRRC同步輻射中心會議 
第3週
9/25  Structural and Chemical Properties of Biological Macromolecules 
第4週
10/2  Protein Crystallography 
第5週
10/9  Electron Microscopy 
第6週
10/16  Principle of Nuclear Magnetic Resonance Spectroscopy:
(I)Biomolecular NMR technique 
第7週
10/23  Principle of Nuclear Magnetic Resonance Spectroscopy:
(II)Multi-dimesional NMR for protein determination 
第8週
10/30  Structural Bioinformatics 
第9週
11/6  Mid-term 
第10週
11/13  (農化導論)Biophysical Methods to Probe Non-covalent Molecular Interaction (I):Circular Dichroism, UV and Fluorescence Spectroscopy  
第11週
11/20  Biophysical Methods to Probe Non-covalent Molecular Interaction (II):Surface Plasmon Resonance, ITC and Analytical Ultracentrifugation 
第12週
11/27  Structural Basis of Signal Transduction and Post-translation Modification 
第13週
12/4  Molecular Enzymology 
第14週
12/11  Protein/peptide interaction with membrane 
第15週
12/18  (AsCA 2019)Structural Features of Receptors and ligands 
第16週
12/25  Structural View of Protein-DNA Recognition in Gene Regulation 
第17週
1/1  (元旦)Molecular Docking and Bioinformatics Approach:Strategies for Drug Discovery, Rational Drug Design versus Drug screen 
第18週
1/8  final-exam
PD-1/PD-L1
1. Lin, D.Y., Tanaka, Y., Iwasaki, M., Gittis, A.G., Su, H.P., Mikami, B., Okazaki, T., Honjo, T., Minato, N., and Garboczi, D.N. (2008). The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. Proc. Natl. Acad. Sci. USA 105, 3011–3016. (莊秉璋)
2.Magiera-Mularz K, Skalniak L, Zak KM, Musielak B, Rudzinska-Szostak E, Berlicki Ł, Kocik J, Grudnik P, Sala D, Zarganes-Tzitzikas T, Shaabani S, Dömling A, Dubin G, Holak TA. (2017). Bioactive Macrocyclic Inhibitors of the PD-1/PD-L1 Immune Checkpoint. Angew Chem Int Ed Engl. 2017 Oct 23;56(44):13732-13735. (江柏辰)
3. Zhang, F., Wei, H., Wang, X., Bai, Y., Wang, P., Wu, J., Jiang, X., Wang, Y., Cai, H., Xu, T., and Zhou, A. (2017). Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade. Cell Discov. 3, 17004. (羅安琦)

PARylation
4. Eustermann,S., Wu,W.F., Langelier,M.F., Yang,J.C., Easton,L.E., Riccio,A.A., Pascal,J.M. and Neuhaus,D. (2015) Structural basis of detection and signaling of DNA Single-Strand breaks by human PARP-1. Mol. Cell, 60, 742–754. (廖婕伶)
5. Langelier,M.F., Zandarashvili,L., Aguiar,P.M., Black,B.E. and Pascal,J.M. (2018) NAD+ analog reveals PARP-1 substrate-blocking mechanism and allosteric communication from catalytic center to DNA-binding domains. Nat. Commun., 9, 844. (許會卿)
6. Slade,D., Dunstan,M.S., Barkauskaite,E., Weston,R., Lafite,P., Dixon,N., Ahel,M., Leys,D. and Ahel,I. (2011) The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase. Nature, 477, 616–620. (王柏筌)

BrD and drug discovery
7. Dhalluin, C. et al. Structure and ligand of a histone acetyltransferase bromodomain. Nature 399, 491–496 (1999). (楊芥)
8. Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 1067–1073 (2010). (吳松晏)
9. Nicodeme, E. et al. Suppression of inflammation by a synthetic histone mimic. Nature 468, 1119–1123 (2010). (范雅清)

Polyketide synthethase
10. S. Dutta, J.R. Whicher, D.A. Hansen, W.A. Hale, J.A. Chemler, G.R. Congdon, et al. Structure of a modular polyketide synthase Nature, 510 (2014), pp. 512-517 (郭芃妤)
11. D.A. Herbst, R.P. Jakob, F. Zähringer, T. Maier. Mycocerosic acid synthase exemplifies the architecture of reducing polyketide synthases
Nature, 531 (2016), pp. 533-537 (鄭宸享)
12. J.R. Whicher, S. Dutta, D.A. Hansen, W.A. Hale, J.A. Chemler, A.M. Dosey, et al.
Structural rearrangements of a polyketide synthase module during its catalytic cycle
Nature, 510 (2014), pp. 560-564 (張書榕)

Crispr
13. Jinek M, Jiang F, Taylor DW, Sternberg SH, Kaya E, et al. 2014. Structures of Cas9 endonucleases reveal RNA-mediated conformational activation. Science 343(6176): 1247997 (莊享愷)
14. Kim, I., Jeong, M., Ka, D. et al. Solution structure and dynamics of anti-CRISPR AcrIIA4, the Cas9 inhibitor. Sci Rep 8, 3883 (2018) (陳節昕)