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Beyond Linus Pauling:
Conformation dependence
of ideal geometry in proteins
Donald S. Berkholz
P. Andrew Karplus lab
What is ideal geometry?
α α
R
R
NH2
Where do you encounter ideal geometry?
Where do you encounter ideal geometry?
Where do you encounter ideal geometry?
Where do you encounter ideal geometry?
Where do you encounter ideal geometry?
Ideal geometry paradigm is limited
N-Cα-C
A new paradigm
N-Cα-C
Why is this important?
RMSD(N-Cα-C)
Engh & Huber = 2.54°
Conformation-Dependent Library = 1.65°
Why is this important?
Our approach
Our approach

Protein Geometry
Database
Our approach

Protein Geometry
Database

≤1.0 Å resolution
Our approach

Protein Geometry
Database

≤1.0 Å resolution

Residues in PGD

19,516 (≤90% ID)

16,975 (≤25% ID)
Our approach

Protein Geometry
Database

≤1.0 Å resolution

Residues in PGD

19,516 (≤90% ID)

16,975 (≤25% ID)

Con...
What trends exist?
N-Cα-C
average
φ
ψ
Averages known with high certainty
N-Cα-C
standard
error
ψ
φ
Dependent on local torsion angle
α α
R
R
NH2
Dependent on local torsion angle
C-1
-N-Cα
average
φ
ψ
α α
R
R
119.5 126.0
NH2
Dependent on local torsion angle
N-Cα-C
average
C-1
-N-Cα
average
φ
ψ
φ
ψ
α α
R
R
119.5 126.0 107.5 114.0
NH2
Dependent on local torsion angle
N-Cα-C
average
C-1
-N-Cα
average
Cα-C-N+1
average
φ
ψ
φ
ψ
φ
ψ
α α
R
R
119.5 126.0 107.5 1...
Rationalizing φ = 40-90°
Rationalizing φ = 40-90°
C-1
-N-Cα
average
ψ
ω-1
average
ψ
O-1
-C-1
-N
average
ψ
φ
φ
N-Cα-Cβ
average
ψ
φφ
φ
172.0 189.0
Rationalizing φ = 40-90°
C-1
-N-Cα
average
ψ
ω-1
average
ψ
O-1
-C-1
-N
average
ψ
φ
φ
N-Cα-Cβ
average
ψ
φφ
φ
172.0 189.0
New paradigm for
peptide planarity
PDB: 2cws at 7.0σ
New paradigm for
peptide planarity
ω
average
ω-1
average
φ
φ
ψ
ψ
PDB: 2cws at 7.0σ
172.0 189.0
How could CDL improve refinement?
How does CDL improve refinement?
How does CDL improve refinement?
RMSD(N-Cα-C)
Resolution 2.5 Å 1.7 Å
Engh & Huber 3.23° 3.56°
Conformation-
Dependent
Libr...
Conclusion
N-Cα-C
average
φ
ψ
The old paradigm
110.5 110.5
Conclusion
N-Cα-C
average
ψ
φ
N-Cα-C
average
φ
ψ
The old paradigm The new paradigm
107.5 114.0110.5 110.5
Why is this important?
RMSD(N-Cα-C)
Engh & Huber = 2.39°
Conformation-Dependent Library = 1.50°
Why is this important?
What is the impact of these variations?
Approach to trend analysis
N-Cα-C
average
ψ
φ
Approach to trend analysis
N-Cα-C
average
ψ
φ
Peptide planarity is overexaggerated
Kang 2004
Beyond Linus Pauling: Conformation dependence of ideal geometry in proteins
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Beyond Linus Pauling: Conformation dependence of ideal geometry in proteins

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A presentation I gave at the West Coast Protein Crystallography Workshop, for which I earned the Best Student Talk award.

Published in: Science
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Beyond Linus Pauling: Conformation dependence of ideal geometry in proteins

  1. 1. Beyond Linus Pauling: Conformation dependence of ideal geometry in proteins Donald S. Berkholz P. Andrew Karplus lab
  2. 2. What is ideal geometry? α α R R NH2
  3. 3. Where do you encounter ideal geometry?
  4. 4. Where do you encounter ideal geometry?
  5. 5. Where do you encounter ideal geometry?
  6. 6. Where do you encounter ideal geometry?
  7. 7. Where do you encounter ideal geometry?
  8. 8. Ideal geometry paradigm is limited N-Cα-C
  9. 9. A new paradigm N-Cα-C
  10. 10. Why is this important? RMSD(N-Cα-C) Engh & Huber = 2.54° Conformation-Dependent Library = 1.65°
  11. 11. Why is this important?
  12. 12. Our approach
  13. 13. Our approach  Protein Geometry Database
  14. 14. Our approach  Protein Geometry Database  ≤1.0 Å resolution
  15. 15. Our approach  Protein Geometry Database  ≤1.0 Å resolution  Residues in PGD  19,516 (≤90% ID)  16,975 (≤25% ID)
  16. 16. Our approach  Protein Geometry Database  ≤1.0 Å resolution  Residues in PGD  19,516 (≤90% ID)  16,975 (≤25% ID)  Conformation-Dependent Library
  17. 17. What trends exist? N-Cα-C average φ ψ
  18. 18. Averages known with high certainty N-Cα-C standard error ψ φ
  19. 19. Dependent on local torsion angle α α R R NH2
  20. 20. Dependent on local torsion angle C-1 -N-Cα average φ ψ α α R R 119.5 126.0 NH2
  21. 21. Dependent on local torsion angle N-Cα-C average C-1 -N-Cα average φ ψ φ ψ α α R R 119.5 126.0 107.5 114.0 NH2
  22. 22. Dependent on local torsion angle N-Cα-C average C-1 -N-Cα average Cα-C-N+1 average φ ψ φ ψ φ ψ α α R R 119.5 126.0 107.5 114.0 114.5 119.5 NH2
  23. 23. Rationalizing φ = 40-90°
  24. 24. Rationalizing φ = 40-90° C-1 -N-Cα average ψ ω-1 average ψ O-1 -C-1 -N average ψ φ φ N-Cα-Cβ average ψ φφ φ 172.0 189.0
  25. 25. Rationalizing φ = 40-90° C-1 -N-Cα average ψ ω-1 average ψ O-1 -C-1 -N average ψ φ φ N-Cα-Cβ average ψ φφ φ 172.0 189.0
  26. 26. New paradigm for peptide planarity PDB: 2cws at 7.0σ
  27. 27. New paradigm for peptide planarity ω average ω-1 average φ φ ψ ψ PDB: 2cws at 7.0σ 172.0 189.0
  28. 28. How could CDL improve refinement?
  29. 29. How does CDL improve refinement?
  30. 30. How does CDL improve refinement? RMSD(N-Cα-C) Resolution 2.5 Å 1.7 Å Engh & Huber 3.23° 3.56° Conformation- Dependent Library 1.32° 1.54°
  31. 31. Conclusion N-Cα-C average φ ψ The old paradigm 110.5 110.5
  32. 32. Conclusion N-Cα-C average ψ φ N-Cα-C average φ ψ The old paradigm The new paradigm 107.5 114.0110.5 110.5
  33. 33. Why is this important? RMSD(N-Cα-C) Engh & Huber = 2.39° Conformation-Dependent Library = 1.50°
  34. 34. Why is this important?
  35. 35. What is the impact of these variations?
  36. 36. Approach to trend analysis N-Cα-C average ψ φ
  37. 37. Approach to trend analysis N-Cα-C average ψ φ
  38. 38. Peptide planarity is overexaggerated Kang 2004

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