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

• 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.

So far...

• 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, ...

Last class...

• Peptide bond conformation
• α

α α α

• β

β β β

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

Amino Acids (2012) 42:ASAP

Distribution of ω ω ω ω in high- resolution protein structures ω ω ω ω

Cα α α α-C-N-Cα α α α

• Occurrence of cis peptide bonds in proteins

Amino Acids (2012) 42:ASAP

ω ω ω ω

Cα α α α-C-N-Cα α α α Xaa1 Xaa2

Percentage calculated with respect to the frequency of occurrence of amino acids

• Cis peptide bond: N- or C-terminus of proline?
• α

α α α

• β

β β β

• γ

γ γ γ δ δ δ δ

• Peptide bond at the C-terminus of proline:

no special preference for trans or cis Is like any of the other 19 amino acid residues

• β

β β β

• γ

γ γ γ δ δ δ δ α α α α

• Peptide bond at the N-terminus of proline:

Cis-peptide bond occurs more frequently compared to other 19 amino acid residues

• Xxx – non-prolyl peptide bond

α α α α α α α α

• α

α α α α α α α

• Xxx – prolyl peptide bond

α α α α α α α α δ δ δ δ

• α

α α α α α α α δ δ δ δ ! ! "! #! $%&'%($%) *++,-

• .

, .

• '%( $%(%%/0(0%1*%$23
• '%($(%0* %+

(4%&04%*+3

Cis peptide bond – why often with proline?

• 5

, . #

• .

5

Ribonuclease A (6RSA)

,6α

α α α 7 .6δ δ δ δ + %+ &%&+

6α

α α α 7 .6α α α α + %+ &%&+

,6α

α α α 7 .6α α α α

+%+ & %&+ 6α

α α α 7 .6δ δ δ δ

+%+ & %&+

Cis peptide bond – why often with proline?

• Preference for trans conformation: steric effect alone?

Protein Sci. (2003) 12:1188

Figure 1 Figure 3

Extent of contribution: depends on substituents, conformation, solvent, ... (e.g.,

• Org. Lett. (2006) 8:4695)