lecture 12: introduction to protein structure; structure ......courtesy of wenqing xu et al. and...

72
1 Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited. Used with permission. Source: Barabási, Albert-László, Natali Gulbahce, et al. "Network Medicine: A Network-based Approach to Human Disease." Nature Reviews Genetics 12, no. 1 (2011): 56-68.

Upload: others

Post on 13-Feb-2020

19 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

����������������

����� �������� �������� 1

Courtesy of Wenqing Xu et al. and RCSBProtein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited. Used with permission.

Source: Barabási, Albert-László, Natali Gulbahce, et al."Network Medicine: A Network-based Approach to Human Disease."Nature Reviews Genetics 12, no. 1 (2011): 56-68.

Page 2: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

   

  

• L12�P�r�rp��t�u���r��tp�r�����rpt�rtp��� �rpt�rtp��&�tb�p�������&����� ��u�������

• L13�P�tp����u���bp�r�����rpt�rtp��� • L14�P�tp����u���bp�r������r�p��u����� • L1S�P�u����t��t��r�p(�N�rw�py��� • L16�P�tp�r����r�r�p��u���N�rw�py��� • L17�P�&�tbtr�r���N�rw�py���������

2

Page 3: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

L��rtp��12�

r�rp��t�u���r��bp�r�����rpt�rtp��

4�

3

Page 4: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

.��. �.���

������

4

Page 5: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

5

© Cold Spring Harbor Laboratory Press. All rights reserved. This content is excluded from our CreativeCommons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Source: Pavletich, Nikola P., Kristen A. Chambers and Carl O. Pabo. "The DNA-binding Domain of p53

Contains the Four Conserved Regions and the Major Mutation Hot Spots." Genes & Development 7, no.

12b (1993): 2556-64.

5

Page 6: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

© American Association for the Advancement of Science. All rights reserved. This content is excludedfrom our Creative Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Source: Cho, Yunje, Svetlana Gorina, et al. "Crystal Structure of a p53 Tumor Suppressor-DNA

Complex: Understanding Tumorigenic Mutations." Science 265, no. 5170 (1994): 346-55.

6

Page 7: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

��

��

��

��

��

htb://www/p��r/�p�/b�r

XPp�(�873434� ���tu���N�t�84323� E���rp������p����b(�8S22� �����P�r�r��N�t�8S6� H(rp���8S2� N�trp���t�3p��u���843� F�r�p�t�3p��u���837� E���rp���&p(�r�����p�bh(�834� ���tu������t�p����832� Orh�p�823�

7

Page 8: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

XPp�(�����N�t�

© Project Crystal. All rights reserved. This content is excluded from our CreativeCommons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

8

Page 9: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

N�t�

htb://www/t����p��r/�p�/�

9

© Jens Meller. All rights reserved. This content is excluded from our CreativeCommons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Courtesy of Kjaergaard on wikipedia. Courtesy of MartinSaunders on wikipedia.

Photograph in the public domain. Photograph in the public domain.

9

Page 10: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

�rpt�rtp���p������p������r��r��pp���

• B�rh��p(�r�����p�bh(�����N�t���b������� ��tbtr�u�����t�rh����r�� ���rh���rpt�rtp�� 8�p��rpt�rtp����rh�r�r��r���p���w�rh� �yb�p�t��r�����r�/�

10

Page 11: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

tp����u����rpt�rtp��

• &�����(�u���r��rh����tbtr�u������h��������� �t���r�pbp�u���XPp�(�����N�t���r��

• A�y�(�r�b�������tp����rtp���

11

Page 12: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

�   

  

Challenges of Structural Bioinformaticscourtesy of Russ Altman & Jonathan Dugan

in Structural Bioinformatics, Philip E. Bourne & Helge Weissig, editors

1/ �rpt�rtp�����r���p����r������p�P����ur��bb�(��rp��������p�rht�� 2/ ���p�h��b����������u�t�t�/�� ��r�� 3/ �rpt�rtp�������r�pt�����r(�bh(������������trr���w�(�rh�r�p����r��

��tb�� ��u��� 4/ Htt���p�/���tbtr�p���r�pt�����r���rpt�rtp��8p��t�����u���p�/�

���p����r�����p��p�p(���3�p��r� S/ Eyb�p�t��r����rpt�rtp�����r���p���tb�pt��r�������tb��r�� 6/ tp�r�����p���r������r�pt���t��rpt�rtp��t�(�h�p��p�p(������t���p�

��bt�������������r��h�p��r������ut(� 7/ W�����ur�y��w�tt�h��r�tr���t����p������������t��tb�pr��r�

bp�r����� 3/ �rpt�rtp���r�����(�t�p�rh��t��r�b�pr�����p�r���b�pr���t���wh����P�

����tr�(����rp��y(�

12

Page 13: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

t����b��r���t�r�p����t�p���r�������� bp�t�p(���������p(��r�pu�p(� �rpt�rtp�����bh��h��������r�r�� �h��r�������t�p��

13

Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission.

13

Page 14: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

������

u�r�r�� y��w�rh�� �t����

F��tp��11/13������p���r�������B�tt�

© Garland Science. All rights reserved. This content is excluded from our Creative Commons license. For more information,see http://ocw.mit.edu/help/faq-fair-use/.

Source: Figure 11.18 in Zvelebil, Marketa J., and Jeremy O. Baum. "Understanding Bioinformatics." Garland Science, 2008.

acids  

14

Page 15: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

�htb://www/p��r/�p�/b�r

16�

Courtesy of RCSB Protein Data Bank. Used with permission.15

Page 16: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

17� Courtesy of RCSB Protein Data Bank. Used with permission.

16

Page 17: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

   

t���p�r�����rpt�rtp���

• p�b��u������t��r�� • y�(������p����r��� • ��r�p�������p����r���

17

Page 18: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Courtesy of RCSB Protein Data Bank. Used with permission.

18

Page 19: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

•� •� •� �

19

Page 20: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

20

Page 21: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

���� �

x� v� z� B�

H��h�p��t����t�B���pp��b����r��t�p��rh�pt���t�u���8p�����1P111�� htb://www/p��r/�p�/b�r/111/�r�u�111/��-b-��t��u�������t�����/L��y���P�rP�rpt�rtp��/���p����r��/hrt�

t�p���r����/� 21

Page 22: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

r�r�p�������p����r���

22

© source unknown. All rights reserved. This content is excluded from our Creative

Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

22

Page 23: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

23

© Annual Reviews. All rights reserved. This content is excluded from our Creative Commonslicense. For more information, see http://ocw.mit.edu/help/faq-fair-use/.Source: Orengo, Christine A., and Janet M. Thornton. "Protein Families and their Evolution--AStructural Perspective." Annual Review Biochemistry 74 (2005): 867-900.

Page 24: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  

&�tb�p�����rpt�rtp��� • N����r���� ���

��pp��b��������r�t�/� • Fp�bt��r�(����(����tr��r��t�

�r�t�:� • t���P�h���� • h��p(��r�t��

• ����t����t��t�r(�p����� r��(�rp���t�pt�u����

RMSD(a, b) = 1 n

aix − bix( )2 + aiy − biy( )

2 + aiz − biz( )2⎡

⎣⎢ ⎤ ⎦⎥

i=1

n

© source unknown. All rights reserved. This content is excluded from our Creative

Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

24

Page 25: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

V)�.����.��

25

Page 26: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

26

Page 27: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

�r�r����rpt�rtp���p�����p��u��t���t�� �����.�

I � Courtesy of Nature Publishing Group. Used with permission.

Source: Dill, Ken A., and Hue Sun Chan. "From Levinthal to Pathways to Funnels."

Nature Structural Biology 4, no. 1 (1997): 10-9.

27

Page 28: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

t�r��u���E��p�(��t���tp�r����

Physicist   StaEsEcian  

28

Page 29: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  

t�r��u���E��p�(��t���tp�r����

• t���p�r��bh(������t�p���� • Ebt�u����t�(�r��

�bbp�y�t�r���rtr�p�bp����r� ����u �r���t�p����

CH�MMM

Physicist   StaEsEcian  

29

Page 30: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  

  

t�r��u���E��p�(��t���tp�r����

• t���p�r��bh(������t�p���� • t���p�r���r��pp�u���� • Ebt�u����t�(�r�� • N�������r��t���p�r����

�bbp�y�t�r���rtr�p�bp����r� �p������t��r�u�u���� ����u �r���t�p���� bp�b�pu���

CH�MMM

Physicist   StaEsEcian  

Rose2a  

30

Page 31: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  

CH�MMM�

  

t�r��u���E��p�(��t���tp�r����

• t���p�r���r��pp�u���� • N�������r��t���p�r����

�p������t��r�u�u���� bp�b�pu���

• t���p�r��bh(������t�p���� • Ebt�u����t�(�r��

�bbp�y�t�r���rtr�p�bp����r� ����u �r���t�p����

Physicist   StaEsEcian  

Rose2a  

31

© source unknown. All rights reserved. This content is excluded from our Creative

Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.31

Page 32: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  

CH�MMM�

  

M� �� �

t�r��u���E��p�(��t���tp�r����

• t���p�r��bh(������t�p���� • t���p�r���r��pp�u���� • Ebt�u����t�(�r�� • N�������r��t���p�r����

�bbp�y�t�r���rtr�p�bp����r� �p������t��r�u�u���� ����u �r���t�p���� bp�b�pu���

Physicist   StaEsEcian  

“Data  don’t  make  any  sense,  we  will  have  to  resort  to  sta<s<cs  

32

© source unknown. All rights reserved. This content is excluded

from our Creative Commons license. For more information, seehttp://ocw.mit.edu/help/faq-fair-use/.

Courtesy of http://vadlo.com/. Used with permission.

Page 33: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

&HAt���E��p�(�Ft��u���

htb://www/�h�pttrtr�p���/�p�/����y/bhb/ h��E��p�(�Ft��u�� �

© source unknown. All rights reserved. This content is excluded from our Creative

Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

http://cbio.bmt.tue.nl/pumma/index.php/Theory/Potentials33

Page 34: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

&HAt���E��p�(�Ft��u����r������

htb://www/�h�pttrtr�p���/�p�/����y/bhb/ h��E��p�(�Ft��u��http://cbio.bmt.tue.nl/pumma/index.php/Theory/Potentials 34

Page 35: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

35

&HAt���E��p�(�Ft��u����r�����

H�pt�����t�p���� t���r���� ���t�rp(�

© C. R. Nave. All rights reserved. This content is excluded from

our Creative Commons license. For more information, seehttp://ocw.mit.edu/help/faq-fair-use/.

htb://www/�h�pttrtr�p���/�p�/����y/bhb/ h��E��p�(�Ft��u��http://cbio.bmt.tue.nl/pumma/index.php/Theory/Potentials

35

Page 36: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

�&HAt���E��p�(�Ft��u����r�����

htb://www/�h�pttrtr�p���/�p�/����y/bhb/ h��E��p�(�Ft��u��http://cbio.bmt.tue.nl/pumma/index.php/Theory/Potentials

36

Page 37: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

�������

&HAt���E��p�(�Ft��u���� ���Pr�����

N��Pr������r�pt�:� L����p��I�����

E���rp��r�u���

 and  

37

Page 38: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

�&HAt���E��p�(�Ft��u���� ���Pr�����

38

© source unknown. All rights reserved. This content is excluded from our Creative

Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Page 39: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

V)�.����.��

39

Page 40: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

t���t��E��p�(�Ft��u��� ���b����t�rp(� y����

X 40

Page 41: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

t���t��E��p�(�Ft��u��� t�r�t�p�:� ��������p�r���������wh��� r�����p�r�r��

41

Source: Kuszewski, John, Angela M. Gronenborn, et al. "Improvements and Extensions

in the Conformational Database Potential for the Refinement of NMR and X-ray Structures

of Proteins and Nucleic Acids." Journal of Magnetic Resonance 125, no. 1 (1997): 171-7.

Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission.

Page 42: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Fp�bt���(��t��r�r���

Etb�p�����b�r��u������p�(�

Courtesy of Steven Combs (PDF). Used with permission.

42

Page 43: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Courtesy of Jeffrey J Gray (PDF). Used with permission.

43

Page 44: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

p�p(���t���p�r��bh(�����r�p��w�

44

Courtesy of Jeffrey J Gray (PDF) . Used with permission.

Courtesy of Steven Combs (PDF). Used with permission.

44

Page 45: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Courtesy of Steven Combs (PDF). Used with permission.

45

Page 46: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

tp�t�p���tt���p�r�u����

46

© Wiley-Liss. All rights reserved. This content is excluded from our Creative Commons

license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

Source: Mendes, Joaquim, António M. Baptista, et al. "Improved Modeling of Side‐chains

in Proteins with Rotamer-based Methods: A Flexible Rotamer Model." Proteins: Structure,

Function, and Bioinformatics 37, no. 4 (1999): 530-43.Courtesy of Jane S. Richardson. License: CC-BY.

46

Page 47: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

����p�u������p�p(�h�p��t�p�rh��bh(�����r��

47

Page 48: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

48

Page 49: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

���p�u������p�p(�h�p��t�p�rh��bh(�����r�� ���(�t�p�rh���r�u�u�����

Etb�p��������tu��� solv RefΔGi = Δ Gi −∑ fi ( )rij Vj

Eyb�p�t��r���(� ��r�pt����� ���p�u���� �t��p�tb� wh���tt��(�

��r�p��u����t� �p�tb�t����p��r� �p�tb����t��yb����/�

8Fp�t�rp���t�p� �yb�p�t��r���

j i≠

V��tt���t�� ����hr�p����

t��r����P ��b�����r� tt��u���t�p��

49

Page 50: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Courtesy of Jeffrey J Gray (PDF). Used with permission.

50

Page 51: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  

�ttt�p(�

• tp�r�����rpt�rtp�����t����������r�����(� • Eyb�p�t��r���r��h��bt�����p������rp���r�����r� �rpt�rtp���

• &�tbtr�u�����t�rh�����������r����r�pbp�r� ����rp���r��

• w��t�����bbp���h��:�bh(�����������r�u�u����

51

Page 52: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Wh�r�w�p��rh��y�(���tb�� ��u�����t� rh���r�u�u�����bbp���h-�

© source unknown. All rights reserved. This content is excluded from our Creative

Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

52

Courtesy of http://vadlo.com/. Used with permission.

Page 53: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Wh�r�w�p��rh��y�(���tb�� ��u�����t� rh���r�u�u�����bbp���h-�

• F�y������t�rp(�

• t���p�r��p�r�t�p��

• �r�u�u����b�r��u��� Fp�bt���(��t��r�r���

Etb�p�����b�r��u������p�(�

53

Source: Kuszewski, John, Angela M. Gronenborn, et al."Improvements and Extensions in the Conformational

Database Potential for the Refinement of NMR and X-ray

Structures of Proteinsand NucleicAcids." Journal of

Magnetic Resonance 125, no. 1 (1997): 171-7.

53

Courtesy of Elsevier, Inc., http://www.sciencedirect.com.Used with permission.

Page 54: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

A�rh�t�hr��yb�p�t��r:� Wh��h��rpt�rtp��t�r�h�������bt����-�

rQVFL�AtttAtEV��rY tNLrLQY�t���LQ�rLt tALutFEN�LAtu�Ft AAt��YtrtH AFE��rrV Q �t�FtV�LrEAAtN HFttLuLE AtAFuH�L A AALA&FFAtE�A N��

Courtesy of RCSB Protein Data Bank. Used with permission.

54

htb://www/p��r/�p�/b�r/�t����/2ph3�r���p�S11/tb�

� htb://www/p��r/�p�/b�r/�t����/1btb�r���p�S11/tb��54

Page 55: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

p�/�

• H�w���t���(�t�t������p�(�tt��u����r�� ���u��t��h-�– L�ru�����tt�������t�rh���rpt�rtp������rh����pp��r� ���/�

– Wh��h��h�t���h�p��rh����w�p�b�r��u������p�(-�– Wh�r����(�t�rh��y�h�bb�������bp��u��-�

Courtesy of RCSB Protein Data Bank. Used with permission.

55

Page 56: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  

  

p�/�

• rt������t�rh���rpt�rtp������rh����pp��r����:� – N����r����r�pt����������h�������t�pt�u���� r�t�p������t��u���b�r��u���

• rt�r�t�p��rpt�rtp��������(��bbp�y�t�r�:� – N����r��p� ���r��yr��������������h����� p�r/�

Courtesy of RCSB Protein Data Bank. Used with permission.

56

Page 57: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

hp�������8t����p������u����

rQVFL�AtttAtEV��rY tNLrLQY�t���LQ�rLt tALutFEN�LAtu�Ft AAt��YtrtH AFE��rrV Q �t�FtV�LrEAAtN HFttLuLE AtAFuH�L A AALA&FFAtE�A N��

Courtesy of RCSB Protein Data Bank.Used with permission.

57

Page 58: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Orh�p�bp����u���bp�r��t�� �������p(��rpt�rtp��

rQVFL�AtttAtEV��rY tNLrLQY�t���LQ�rLt tALutFEN�LAtu�Ft AAt��YtrtH AFE��rrV Q �t�FtV�LrEAAtN HFttLuLE AtAFuH�L A AALA&FFAtE�A N��

��t�����rpt�rtp��

��p���3t��rpt�rtp��

58

Courtesy of RCSB Protein Data Bank.Used with permission.

58

Page 59: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

��t��h��r�p(�

�NrVA&�1�p�����������14S1� Courtesy of U.S. Department of the Army Ballistic Research Report. In the public domain.

59

© The estate of the authors. All rights reserved.

This content is excluded from our Creative

Commons license. For more information, see

http://ocw.mit.edu/help/faq-fair-use/.

Source: Pauling, Linus, Robert B. Corey, and Herman R.Branson. "The Structure of Proteins: Two Hydrogen-bonded Helical Configurations of the Polypeptide

Chain." Proceedings of the National Academy ofSciences 37, no. 4 (1951): 205-211.

Page 60: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

   

  

64�

��t��h��r�p(�

• t�b�p�t������� • ��(������hr�wh�����(�������r�������y�� • tp�������r(���r���t�h�p��w�py�������u��� �yb�p�t��r�����r��

• t����p�b�bu���r����� • ��y�t����h(�p�����r�����

60

© The estate of the authors. All rights reserved.

This content is excluded from our Creative

Commons license. For more information, see

http://ocw.mit.edu/help/faq-fair-use/.

Source: Pauling, Linus, Robert B. Corey, and Herman R.Branson. "The Structure of Proteins: Two Hydrogen-bonded Helical Configurations of the Polypeptide

Chain." Proceedings of the National Academy ofSciences 37, no. 4 (1951): 205-211.

Page 61: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Source: Ramachandran, G. N., C. T. Ramakrishnan, et al. "Stereochemistry of Polypeptide

Chain Configurations." Journal of Molecular Biology 7, no. 1 (1963): 95-9.

© source unknown. All rights reserved. This content is excluded

from our Creative Commons license. For more information,

see http://ocw.mit.edu/help/faq-fair-use/.

61

Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission.

Page 62: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

B��bh(������I�tp����V��tt��7��r��t��2����p�h�1467��t�����121�13S�

62

Page 63: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

© source unknown. All rights reserved. This content is excluded from our Creative

Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

63

Page 64: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

• A���tr�����r�u�u���� ��r��tp�t�rh���t������r� �t�y��w���rpt�rtp���

• t� �����bp�b����r(�� t�p�h���y�t�pt�u���

• &pt���pt����r��bp����r� h�������p�������

© American Chemical Society. All rights reserved. This content is excludedfrom our Creative Commons license. For more information, seehttp://ocw.mit.edu/help/faq-fair-use/.

64

Source: Chou, Peter Y., and Gerald D. Fasman. "Conformational Parameters

for Amino Acidsin Helical, β-sheet, and Random Coil Regions Calculated from

Proteins." Biochemistry 13, no. 2 (1974): 211-22.

Page 65: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  �

• Helix Nucleaton/��L���r����t�r�p���t�t�tp��tr��t���y� p����t���w�rh���h��h�bp�b����r(�t�p�t�pt����h������/�����

• h�p���p���b������������t�p�A�b�����H���wh��h�w��y�(� �t����r������t�p� (p��A����tp������u�(�wh��h��p�� �������p���h���y�rp��y�p�/�

• Helix Terminaton/��Eyr����rh��h����������t��r���� �o�� ��p��u����t�u��r�pt���r���r(�r�rp�b�bu����w�rh���w� �p�p����h�������bp�b����r(����p��/���

• tp�������r����tp����rh����bh��h���y/�

65

Page 66: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

t61%����tp��(�

66

Page 67: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  

• Obu�����p������:� – &h�br�p�12��t��p���r�������B�tt�h��������r������ ����p�bu����t��tpp��r�����p�rht��

67

Page 68: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

Orh�p�bp����u���bp�r��t�� �������p(��rpt�rtp��

rQVFL�AtttAtEV��rY tNLrLQY�t���LQ�rLt tALutFEN�LAtu�Ft AAt��YtrtH AFE��rrV Q �t�FtV�LrEAAtN HFttLuLE AtAFuH�L A AALA&FFAtE�A N��

��t�����rpt�rtp��

��p���3t��rpt�rtp��

Courtesy of RCSB Protein Data Bank.Used with permission.

68

Page 69: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

�����.�

��p���3t��rpt�rtp��

&�tbtr�u�����tp�r����F�������

r��bp����b����w�����ur��p�����������r�pu����rpt�rtp�/� rQVFL�AtttAtEV��rY tNLrLQY�t���LQ�rLt tALutFEN�LAtu�Ft AAt��YtrtH AFE��rrV Q �t�FtV�LrEAAtN HFttLuLE AtAFuH�L A AALA&FFAtE�A N��

Courtesy of RCSB Protein Data Bank.Used with permission.

Courtesy of Nature Publishing Group. Used with permission.Source: Dill, Ken A. and Hue Sun Chan. "From Levinthal to Pathways to Funnels."

Nature Structural Biology 4, no. 1 (1997): 10-9.

69

Page 70: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

�r�u�u������p�/�th(�����r��

© source unknown. All rights reserved. This content is excluded from our Creative

Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/.

70

Courtesy of http://vadlo.com/. Used with permission.

Page 71: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

  

�r�u�u������p�/�th(�����r��

M� �� • L�p�p�����p�p(rh����w��

y��w��r�tr��y��u��� �rpt�rtp����t�bp�r��������� b�bu����r��rt�����r�pu��� t������

• t� ���t�������y��w�����P r�����b�r��u���

D��.. �� • tONu �&HEA �� • O��(�t���bh(������t�p���/� • F����bp�r�����r(���tt��u���

rh�����p�rp��bp������

71

Page 72: Lecture 12: Introduction to Protein Structure; Structure ......Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. Courtesy of Macmillan Publishers Limited

MIT OpenCourseWarehttp://ocw.mit.edu

7.91J / 20.490J / 20.390J / 7.36J / 6.802J / 6.874J / HST.506J Foundations of Computational and Systems BiologySpring 2014

For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms.