作業1
Assignment #1

1. 列出alpha-螺旋與beta平板結構的phi/psi角範圍？
Give the ranges of backbone Phi/PSi angle ranges found for alpha helical regions in proteins. For beta strand conformations.

2. 請問在B&T書中圖十七a與b所列的值各為何？
What are the origins of the values in B&T figures 1.7a and 1.7b?

3. 請問在球蛋白晶體結構中alpha螺旋與beta平板的平均長度各為何？
What is the average length of alpha helices found in crystal structures of globular proteins? Beta-strands?

4. Pauling, Corey 與 Branson所指出的alpha螺旋掌性為何？ B&T 一書中所提alpha螺旋掌性為何？
What is the handedness of the helices shown in Pauling, Corey and Branson? The handedness of the alpha helices in the B&T reading?

閱讀資料
Readings:

1. B&T一書。第一章
Branden and Tooze. Chapter 1 (2nd edition).

2. Alpha螺旋：
Alpha Helices:

• Pauling, Linus, Robert B. Corey以及H. R. Branson等人發表於《美國國家科學院院刊》 37 （1951）：205-210。〈蛋白質結構：兩種胜肽鏈的氫鍵連結螺旋構型〉
  Pauling, Linus, Robert B. Corey, and H. R. Branson. "The Structure of Proteins: Two Hydrogen Bonded Helical Configurations of the Polypeptide Chain." Proc. Nat. Acad. Sci. 37 (1951): 205-210.
• B&T一書。13-26頁
  Branden and Tooze. pp. 13-26.

3. X射線繞射的概觀：Overview of X-ray diffraction methods:

• B&T一書。第十八章 373-386頁
  Branden and Tooze. Chapter 18, pp. 373-386.

作業3
Assignment #3

1. Pauling, Corey 與 Branson （1951年） 構出兩個螺旋模型滿足化學與立體條件。請以列表的方式呈現兩個模型的1.氫鍵長 2.每圈有幾個胺基酸 3.每個胺基酸的升幅 4.每圈的升幅
Pauling, Corey and Branson (1951) concluded that two helical models satisfied their chemical/steric criteria. Please construct a Table with values of the following features for the two helices proposed.
H-bond length: Residues per turn: Rise per residue: Pitch: (rise/helical turn):

2. 利用手繪、拷貝或是描繪的方式畫一份B&T一書中的圖二（e） ，以黑色標出alpha碳，以藍色標出氮原子 ，並指出胺基端與羧酸端
Draw, copy, or trace a version of figure 2(e) of B&T, with the alpha carbons and Nitrogen atoms clearly labeled or colored (N=blue, C= black). Label the N-and C-termini of this short peptide.

3. 根據Anfinsen, et. al. （1961年）的文章中的一組實驗曲線指出核酸酶的活性的恢復比螺旋結構和雙硫鍵恢復與生成慢。他們是提供那個模型以作說明？
Anfinsen, et. al. (1961) show a set of experimental curves in which the regain of Rnase activity lags behind the regain of helicity and S-S bond formation. Which of their models is offered as an explanation of these phenomena?

4. 呈現出牛胰臟核酸酶A（蛋白資料庫編號1FS3）的分子結構圖*，途中須包含以下特點
Create a single image* that shows the molecular structure of bovine pancreatic ribonuclease A (PDB-ID 1FS3). The image should show:

• 完整的分子結構以緞帶形式呈現並以二級結構上色
  the entire molecule as a ribbon colored by secondary structure,
• 所有四對雙硫鍵：CYS 26-CYS84，CYS40-CYS95，CYS58-110與CYS 65-CYS72 以實心圓柱呈現
  all 4 disulfide bonds: CYS 26-CYS84, CYS40-CYS95, CYS58-110, and CYS 65-CYS72 as solid cylinders,
• 其中一個雙硫鍵：CYS40-CYS95以空間填滿的方式呈現
  one disulfide bond: CYS40-CYS95 as space-filled.
  
  

5. 選一個可以看見三個alpha螺旋與空間填滿模式的雙硫鍵的 角度（不會被beta平板遮住的面）
Choose a point of view in which all three alpha helices and the one space-filled disulfide bond are completely visible, i.e. not obscured by beta-strands.

* 圖不用做的很炫，用'PrintScreen'鍵存圖再把圖貼到文書編輯軟體即可。單色圖就可以了，不要把顏色上得很花
* Nothing fancy is required for the image. Using the 'PrintScreen' button and pasting the screen image into a text editing program is sufficient. Similarly, color hard copy is not essential. A monochrome image will do.

閱讀資料
Readings:

Perutz, Max F. 〈對晶體的熱情〉 《我真該早點讓你生氣一點：科學小品、科學與人性》，1998, 第 209-212頁，冷泉港實驗室
Perutz, Max F. "A Passion for Crystals." I Wish I'd Made you Angrier Earlier: Essays on Science, Scientists & Humanity. Cold Springs Harbor Lab Press, 1998, pp. 209-212.

In B&T一書：
Branden and Tooze:

• 第二章與第三章
  Chapters 2 and 3.
• B&T一書. 第十八章 373-386頁，X射線繞射
  Chapter 18: X-ray diffraction. Pp. 373-386.

先前講義
Previously Handed out:

Pauling, Linus, Robert B. Corey以及H. R. Branson等人發表於《美國國家科學院院刊》37 （1951）: 205-210. 〈蛋白質結構:胜肽鏈的兩種氫鍵連結螺旋構型〉
Pauling, Linus, Robert B. Corey, and H. R. Branson. "The Structure of Proteins: Two Hydrogen Bonded Helical Configurations of the Polypeptide Chain." Proc. Nat. Acad. Sci., USA 37 (1951): 205-210.

Anfinsen, C. B., Edgar Haber, M. Sela,以及F. H. White, Jr. 等人發表於《美國國家科學院院刊》47 （1961）: 1309-1314〈自還原態的多胜肽鏈氧化成自然態的核酸酶的動力學〉
Anfinsen, C. B., E. Haber, M. Sela, and F. H. White, Jr. "The Kinetics of Formation of Native Ribonuclease During Oxidation of the Reduced Polypeptide Chain." PNAS 47 (1961): 1309-1314.

作業5
Assignment #5

1. 仔細閱讀下列兩篇文章：
Read the following two papers carefully:

• O'Shea, Erin, Juli D. Klem, Peter S. Kim以及Tom Alber. 等人發表於《科學》254 （1991）: 539-544. 〈CGN4白胺酸拉鍊的X-射線結構:一個平行雙絞捲曲環圈〉
  O'Shea, Erin, Juli D. Klem, Peter S. Kim, and Tom Alber. “X-ray Structure of the CGN4 Leucine Zipper, a Two-Stranded, Parallel Coiled Coil.” Science 254 (1991): 539-544.
• Cohen, Carolyn, 以及 David A. D. Parry等人發表於《科學》263 （1994）: 488-489〈Alpha-螺旋捲曲環圈:更多的事實與更好的預測〉
  Cohen, Carolyn, and David A. D. Parry. “Alpha-Helical Coiled Coils: More Facts and better Predictions.”
  Science 263 (1994): 488-489.
  

2. 回答下列問題：
Answer the following question:
除了課堂上提到的螺旋間離子對之外，出現在CGN4的螺旋內離子對為何？
What intra-helical ion pairs are present in the GCN4 structure in addition to the inter-helical ion pairs described in lecture?

3. 作一個GCN4 （蛋白質資料庫編碼: 2ZTA）的結構圖來呈現：
Create a single image of the GCN4 (PDB-ID: 2ZTA) structure which shows:

• 兩個環圈的主鍊骨幹以緞帶呈現並依照鏈的不同上色
  the backbones of the two coils depicted as ribbons, colored by chain and,
• 課堂上提到的螺旋間離子對以空間填滿的方式呈現
  the inter-helical ion pairs described in lecture depicted as space-filled models.

閱讀資料
Readings:

Perutz, Max F. 〈我真該早點讓你生氣〉 我真該早點讓你生氣: 科學小品,科學與人性1998, 173-175頁, 冷泉港實驗室
Perutz, Max F. "I wish I’d made you angry earlier." From I wish I’d made you angry earlier: Essays on Science, Scientists & Humanity. Cold Springs Harbor Laboratory Press, 1998, pp. 173-175.

仔細閱讀下列兩篇文章：
Read the following two papers carefully:

O'Shea, Erin, Juli D. Klem, Peter S. Kim以及Tom Alber. 等人發表於《科學》254 （1991）: 539-544. 〈CGN4白胺酸拉鍊的X-射線結構:一個平行雙絞捲曲環圈〉
O'Shea, Erin, Juli D. Klem, Peter S. Kim, and Tom Alber. "X-ray Structure of the CGN4 Leucine Zipper, a Two-Stranded, Parallel Coiled Coil." Science 254 (1991): 539-544.

Cohen, Carolyn, 以及 David A. D. Parry等人發表於《科學》263 （1994）: 488-489〈Alpha-螺旋捲曲環圈:更多的事實與更好的預測 〉
Cohen, Carolyn, and David A. D. Parry. "Alpha-Helical Coiled Coils: More Facts and better Predictions." Science 263 (1994): 488-489.

1. Marquesee & Baldwin一文的圖四,其中的各螺旋結構如果出現在球蛋白中,是否可以穩定地互相依存，為什麼？
Could the helices shown in Figure 4 of Marquesee & Baldwin, dock stably against each other or themselves if they occurred within a globular protein? How, why or why not?

2.

• 列出各種Aurora等人認為可以促進alpha螺旋在胜肽鏈中形成的因素
  List the various contributions promoting the formation of alpha helices in polypeptide chains considered by Aurora et. al.
• 從你的閱讀心得或上課筆記中你是否能舉出任何新的因素或排除或降低某些因素的重要性
  Would you add any additional factors from your reading or lecture notes, or eliminate or reduce the importance of any of theirs?

3. 在Nall文中的圖一，為何a跟b欄的訊號下降而其他四欄卻上升？
In Figure 1 of Nall, why do the signals in a and b decrease, while those in the other four panels increase with time?

閱讀資料
Readings:

Marquesee, Susan, 以及 Robert L. Baldwin.發表於《蛋白質摺疊:遺傳密碼解碼的第二部份》〈水溶液中短胜肽alpha螺旋的生成〉Lila M. Gierasch,與Jonathan King編輯。Washington D.C.: AAAS, 1990。
Marquesee, Susan, and Robert L. Baldwin. "a-Helix Formation by Short Peptides in Water." Protein Folding: Deciphering the Second Half of the Genetic Code. Edited by Lila M. Gierasch, and Jonathan King. Washington D.C.: AAAS, 1990.

Richardson, Jane S.以及 David C. Richardson. 等人發表於《科學》240 （1988）: 1648-1652。在螺旋末端的的某些特定區位對胺基酸的偏好
Richardson, Jane S., and David C. Richardson. "Amino Acid Preferences for specific Locations at the Ends of a Helices." Science 240 (1988): 1648-1652.

Aurora, R., T. P. Creamer, R. Srinivasan以及G. D. Rose等人發表於《生物化學期刊》 272 （1997）: 1413-1416 〈蛋白質摺疊的局部交互作用:來自alpha螺旋的一課〉
Aurora, R., T. P. Creamer, R. Srinivasan, and G. D. Rose. "Local Interactions in Protein folding: Lessons from the a-Helix." JBC 272 (1997): 1413-1416.

Nall, Barry T. 發表於《蛋白質摺疊:遺傳密碼解碼的第二部份》〈脯胺酸異構轉化與其在酵母菌細胞色素C的摺疊的功能〉Lila M. Gierasch,與Jonathan King編輯. Washington D.C.: AAAS, 1990。
Nall, Barry T. "Proline Isomerization and Folding of Yeast Cytochrome c." Protein Folding: Deciphering the Second Half of the Genetic Code. Edited by Lila M. Gierasch, and Jonathan King. Washington D.C.: AAAS, 1990.

Creighton, Thomas E.著 蛋白質：結構與分子性質。第二版. New York: W. H. Freeman & Co., 1993，6.3節，238-244頁。
Creighton, Thomas E. Proteins: Structures and Molecular Properties. 2nd ed. New York: W. H. Freeman & Co., 1993, Section 6.3, pp. 238-244.

研究生閱讀：Graduate Students:

Pain.蛋白質摺疊機制。第三章第五節84-94頁
Pain. Mechanisms of Protein Folding. Chapter 3: Section 5, pp. 84-94.

作業9
Assignment #9

僅有閱讀作業
Reading assignment only.

閱讀資料：
Reading:

Pain. 〈個案研究二: 膠原蛋白三螺旋的摺疊與他天然發生的突變株〉蛋白質摺疊機制第十二章。Jean Baum 與 Barbara Brodsky編輯。
Pain. "Case study 2: Folding of the Collagen Triple-helix and its Naturally Occurring Mutants." Chapter 12 in Mechanisms of Protein Folding. Edited by Jean Baum and Barbara Brodsky.

講義：
Handout:

Kuvaniemi, Helena, Gerard Tromp, 以及 Darwin J. Prockop. 等人發表於《美國聯邦實驗生物學學會會刊》5: 2052-2060〈膠原蛋白基因的突變: 造成人類的常見及罕見的疾病〉
Kuivaniemi, H., G. Tromp, and D. J. Prockop. "Mutations in Collagen Genes: Causes of Rare and Some Common Diseases in Humans." FASEB Journal 5 (1991): 2025-2060.