Quiz 1: Tomorrow from 11 AM to 12 noon GG Building Ground Floor - PowerPoint PPT Presentation

��������������� Quiz 1: Tomorrow from 11 AM to 12 noon GG Building Ground Floor

��������������� So far... � Importance of 3D structures � Realization that molecules / assemblies / ... are all ‘dynamic’ � Conformational changes and the concept of ‘energy landscape’ � Conformation-dependent ‘functions’ � Sequential / concerted conformational changes to perform a function � Rate of conformational inter-conversions: energy barrier, temp. � Torsion angle - quantifies rotation around bonds, which in turn, brings about conformational changes � Energy changes due to bond stretching / angle bending � Population of molecules in different energy minima, ergodic hyp.

��������������� Last class... � Two atoms (other than bonded / geminal), when they come close, repel - van der Waals repulsion � Repulsion is so high that the energy of that conformer will be very high, and consequently such a conformer is not populated (partition function) - essentially, it is a ‘disallowed’ conformation � Virtually an infinite number of conformations are possible, especially for ‘large’ molecules - calculating energy for all these conformers is practically not possible � Limitations of functions / parameters / approach for calculating energies � Hard-sphere approximation: what it is and what is usefulness � Conformation of saccharides: ethane, butane, cyclohexanes, ...

��������������� Peptide bond conformation � β � � α β β β � α α α � � α � α α α � � α � � α α α α α α α � � ��� � ��� ���� �� ���� �� ���� ���� �� �� carbonmonoxymyoglobin (2MB5) N-Carbamoylsarcosine amidohydrolase (1NBA)

��������������� Occurrence of cis peptide bonds in proteins Distribution of ω ω ω ω in high- resolution protein structures ω ω ω ω C α α α α -C-N-C α α α α Amino Acids (2012) 42:ASAP

��������������� Occurrence of cis peptide bonds in proteins Percentage calculated with respect Xaa2 to the frequency of occurrence of Xaa1 amino acids ω ω ω ω C α α α -C-N-C α α α α α Amino Acids (2012) 42:ASAP

��������������� Cis peptide bond: N- or C-terminus of proline? �� � � �� � � � α α α α δ δ δ δ β β β β �� � �� � Peptide bond at the C-terminus of proline: � γ γ γ γ �� � no special preference for trans or cis Is like any of the other 19 amino acid residues �� � � � α � � �� � � � α α α Peptide bond at the N-terminus of proline: δ δ δ δ β β β β �� � �� � Cis-peptide bond occurs more frequently γ γ γ γ �� � compared to other 19 amino acid residues

��������������� Cis peptide bond – why often with proline? Xxx – non-prolyl peptide bond Xxx – prolyl peptide bond � α α ����� � α α ����� α α α α � δ δ ��� δ δ ����� ��"��! �����! �� �� ���, .��� ����� ����� � α α ��� � α α ��� α α α α '�%(� ��$%�(%�%/0(0%1*%$�����23�� � α α ����� α α � α α ��� α α � α α ����� ���#�! α α � α α ��� α α �����! ���� .��� ���� ���� �� �� � δ δ ��� δ δ ����� '�%(������$�(%0*��� %���+ $%�&�'�%(���$%�) *+��+����,-��� �(�4%&04�%*��+����3��

��������������� Cis peptide bond – why often with proline? ���# α 7 .���6� α ���,6� α α α α α α .��� ��+��������%�+� &� α 7 .���6� δ ����6� α .��� α α δ δ δ %�&+� ��+��������%�+� &� %�&+� ���� ���, ���� 5��� 5��� α 7 .���6� δ δ ��+� ����%�+� &�%�&+� α 7 .���6� α α ��+� ����%�+� &�%�&+� ���,6� α ����6� α α α δ δ α α α α Ribonuclease A (6RSA)

��������������� Preference for trans conformation: steric effect alone? Figure 1 Figure 3 Extent of contribution: depends on substituents, conformation, solvent, ... (e.g., Org. Lett. (2006) 8:4695) Protein Sci. (2003) 12:1188