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

1. Beyond Linus Pauling:
Conformation dependence
of ideal geometry in proteins
Donald S. Berkholz
P. Andrew Karplus lab

2. What is ideal geometry?
α α
R
R
NH2

3. Where do you encounter ideal geometry?

4. Where do you encounter ideal geometry?

5. Where do you encounter ideal geometry?

6. Where do you encounter ideal geometry?

7. Where do you encounter ideal geometry?

8. Ideal geometry paradigm is limited
N-Cα-C

9. A new paradigm
N-Cα-C

10. Why is this important?
RMSD(N-Cα-C)
Engh & Huber = 2.54°
Conformation-Dependent Library = 1.65°

11. Why is this important?

12. Our approach

13. Our approach

Protein Geometry
Database

14. Our approach

Protein Geometry
Database

≤1.0 Å resolution

15. Our approach

Protein Geometry
Database

≤1.0 Å resolution

Residues in PGD

19,516 (≤90% ID)

16,975 (≤25% ID)

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. What trends exist?
N-Cα-C
average
φ
ψ

18. Averages known with high certainty
N-Cα-C
standard
error
ψ
φ

19. Dependent on local torsion angle
α α
R
R
NH2

20. Dependent on local torsion angle
C-1
-N-Cα
average
φ
ψ
α α
R
R
119.5 126.0
NH2

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. 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. Rationalizing φ = 40-90°

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. 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. New paradigm for
peptide planarity
PDB: 2cws at 7.0σ

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. How could CDL improve refinement?

29. How does CDL improve refinement?

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. Conclusion
N-Cα-C
average
φ
ψ
The old paradigm
110.5 110.5

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

34. Why is this important?
RMSD(N-Cα-C)
Engh & Huber = 2.39°
Conformation-Dependent Library = 1.50°

35. Why is this important?

36. What is the impact of these variations?

37. Approach to trend analysis
N-Cα-C
average
ψ
φ

38. Approach to trend analysis
N-Cα-C
average
ψ
φ

39. Peptide planarity is overexaggerated
Kang 2004