���������������� Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. ����� 1 �������� 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. �������� • 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 L��rtp��12� r�rp��t�u���r��bp�r�����rpt�rtp�� 4� 3 ������ .��. �.��� 4 © Cold Spring Harbor Laboratory Press. 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: 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 © American Association for the Advancement of 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: 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 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 XPp�(�����N�t� © Project Crystal. All rights reserved. This content is excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/. 8 N�t� Courtesy of MartinSaunders on wikipedia. Photograph in the public domain. Courtesy of Kjaergaard on wikipedia. Photograph in the public domain. � htb://www/t����p��r/�p�/� 9 © Jens Meller. All rights reserved. This content is excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/. �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 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 Challenges of Structural Bioinformatics � courtesy 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 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�� Courtesy of Wenqing Xu et al. and RCSB Protein Data Bank. Used with permission. 13 u�r�r�� y��w�rh�� �t���� acids ������ © 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. 14 F��tp��11/13������p���r�������B�tt� htb://www/p��r/�p�/b�r� 16� 15 Courtesy of RCSB Protein Data Bank. Used with permission. 17� Courtesy of RCSB Protein Data Bank. Used with permission. 16 t���p�r�����rpt�rtp��� • p�b��u������t��r�� • y�(������p����r��� • ��r�p�������p����r��� 17 18 Courtesy of RCSB Protein Data Bank. Used with permission. •� •� •� � 19 20 x� v� z� 21 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����/� r�r�p�������p����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/. 22 23 © Annual Reviews. 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: Orengo, Christine A., and Janet M. Thornton. "Protein Families and their Evolution--A Structural Perspective." Annual Review Biochemistry 74 (2005): 867-900. &�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���� © 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/. n 2 1 ⎡ 2 2⎤ RMSD(a, b) = ( aix − bix ) + ( aiy − biy ) + ( aiz − biz ) ⎥⎦ ∑ ⎢ ⎣ n i=1 24 V)�.����.�� 25 26 �����.� �r�r����rpt�rtp���p�����p��u��t���t�� 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. I 27 � t�r��u���E��p�(��t���tp�r���� Physicist 28 StaEsEcian t�r��u���E��p�(��t���tp�r���� Physicist • t���p�r��bh(������t�p���� • Ebt�u����t�(�r�� �bbp�y�t�r���rtr�p�bp����r� ����u �r���t�p���� CH�MMM� 29 StaEsEcian t�r��u���E��p�(��t���tp�r���� Physicist StaEsEcian • t���p�r��bh(������t�p���� • Ebt�u����t�(�r�� �bbp�y�t�r���rtr�p�bp����r� ����u �r���t�p���� • t���p�r���r��pp�u���� • N�������r��t���p�r���� �p������t��r�u�u���� bp�b�pu��� CH�MMM� 30 Rose2a � t�r��u���E��p�(��t���tp�r���� Physicist • t���p�r��bh(������t�p���� • Ebt�u����t�(�r�� �bbp�y�t�r���rtr�p�bp����r� ����u �r���t�p���� StaEsEcian • t���p�r���r��pp�u���� • N�������r��t���p�r���� �p������t��r�u�u���� bp�b�pu��� CH�MMM� 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/. Rose2a � t�r��u���E��p�(��t���tp�r���� Physicist StaEsEcian • t���p�r��bh(������t�p���� • Ebt�u����t�(�r�� �bbp�y�t�r���rtr�p�bp����r� ����u �r���t�p���� • t���p�r���r��pp�u���� • N�������r��t���p�r���� �p������t��r�u�u���� bp�b�pu��� CH�MMM� 32 © 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/. M� �� � “Data don’t make any sense, we will have to resort to sta<s<cs Courtesy of http://vadlo.com/. Used with permission. &HAt���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/Potentials � 33 htb://www/�h�pttrtr�p���/�p�/����y/bhb/ h��E��p�(�Ft��u�� � &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 &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, see http://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 &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 &HAt���E��p�(�Ft��u�������Pr������ N��Pr������r�pt�:� L����p��I����� � ����� and � E���rp��r�u��� 37 &HAt���E��p�(�Ft��u�������Pr������ © 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/. 38 V)�.����.�� 39 t���t��E��p�(�Ft��u��� 40 X ���b����t�rp(� y���� � t���t��E��p�(�Ft��u��� t�r�t�p�:� ��������p�r���������wh��� r�����p�r�r�� Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission. 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 41 of Proteins and Nucleic Acids." Journal of Magnetic Resonance 125, no. 1 (1997): 171-7. Fp�bt���(��t��r�r��� Etb�p�����b�r��u������p�(� Courtesy of Steven Combs (PDF). Used with permission. 42 Courtesy of Jeffrey J Gray (PDF). Used with permission. 43 Courtesy of Jeffrey J Gray (PDF) . Used with permission. p�p(���t���p�r��bh(�����r�p��w� Courtesy of Steven Combs (PDF). Used with permission. 44 Courtesy of Steven Combs (PDF). Used with permission. 45 tp�t�p���tt���p�r�u���� Courtesy of Jane S. Richardson. License: CC-BY. 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. ���p�u������p�p(�h�p��t�p�rh��bh(�����r�� � 47 48 ���p�u������p�p(�h�p��t�p�rh��bh(�����r�� ���(�t�p�rh���r�u�u����� Etb�p��������tu��� solv i ΔG Eyb�p�t��r���(� ��r�pt����� ���p�u���� �t��p�tb� wh���tt��(� ���p��r� �yb����/� 8Fp�t�rp���t�p� �yb�p�t��r��� 49 = ΔGi Ref − ∑ fi (rij )V j j ≠i t��r����P ��b�����r� tt��u���t�p�� ��r�p��u����t� �p�tb����t� V��tt���t�� ����hr�p���� �p�tb�t� Courtesy of Jeffrey J Gray (PDF). Used with permission. 50 �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 Wh�r�w�p��rh��y�(���tb�� ��u�����t� rh���r�u�u�����bbp���h-� Courtesy of http://vadlo.com/. Used with permission. © 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 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��� Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission. 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. Etb�p�����b�r��u������p�(� 53 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�� htb://www/p��r/�p�/b�r/�t����/2ph3�r���p�S11/tb� � 54 Courtesy of RCSB Protein Data Bank. Used with permission. htb://www/p��r/�p�/b�r/�t����/1btb�r���p�S11/tb�� p�/� Courtesy of RCSB Protein Data Bank. Used with permission. • 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��-� 55 p�/� Courtesy of RCSB Protein Data Bank. Used with permission. • 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/� 56 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 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. 58 ��t��h��r�p(� Courtesy of U.S. Department of the Army Ballistic Research Report. In the public domain. �NrVA&�1�p�����������14S1� 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 of Sciences 37, no. 4 (1951): 205-211. ��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. 64� Branson. "The Structure of Proteins: Two Hydrogen -bonded Helical Configurations of the Polypeptide Chain." Proceedings of the National Academy of Sciences 37, no. 4 (1951): 205-211. © 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/. Courtesy of Elsevier, Inc., http://www.sciencedirect.com. Used with permission. Source: Ramachandran, G. N., C. T. Ramakrishnan, et al. "Stereochemistry of Polypeptide Chain Configurations." Journal of Molecular Biology 7, no. 1 (1963): 95-9. 61 B��bh(������I�tp����V��tt��7��r��t��2����p�h�1467��t�����121�13S� 62 © 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 • 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 excluded from our Creative Commons license. For more information, see http://ocw.mit.edu/help/faq-fair-use/. 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. 64 • 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 t61%����tp��(� 66 • Obu�����p������:� – &h�br�p�12��t��p���r�������B�tt�h��������r������ ����p�bu����t��tpp��r�����p�rht�� 67 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 �����.� &�tbtr�u�����tp�r����F������� 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. 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�� 69 ��p���3t��rpt�rtp�� Courtesy of RCSB Protein Data Bank. Used with permission. �r�u�u������p�/�th(�����r�� Courtesy of http://vadlo.com/. Used with permission. © 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 �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��� 71 D��.. �� • tONu �&HEA �� • O��(�t���bh(������t�p���/� • F����bp�r�����r(���tt��u��� rh�����p�rp��bp������ MIT OpenCourseWare http://ocw.mit.edu 7.91J / 20.490J / 20.390J / 7.36J / 6.802J / 6.874J / HST.506J Foundations of Computational and Systems Biology Spring 2014 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms.