beyond linus pauling: conformation dependence of ideal geometry in proteins
TRANSCRIPT
Beyond Linus Pauling: Conformation dependence
of ideal geometry in proteins
Donald S. BerkholzP. 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)
Conformation-Dependent Library
What trends exist?N-Cα-Caverage
φ
ψ
107.5 114.0
Averages known with high certaintyN-Cα-C
standarderror
ψ
φ0.1 1.1
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-Caverage
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-Caverage
C-1-N-Cα
averageCα-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
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
φφ
N-Cα-Cβaverage
ψ
φφ
φ
109.0 114.0119.5 126.0121.8 123.4
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
φφ
N-Cα-Cβaverage
ψ
φφ
φ
109.0 114.0119.5 126.0121.8 123.4
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 172.0 186.0
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 Library
1.32° 1.54°
Conclusion
N-Cα-Caverage
φ
ψ
The old paradigm
110.5 110.5
Conclusion
N-Cα-Caverage
ψ
φ
N-Cα-Caverage
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 analysisN-Cα-Caverage
ψ
φ
Approach to trend analysisN-Cα-Caverage
ψ
φ
Peptide planarity is overexaggerated
Kang 2004