Emile Zuckerkandl and Linus Pauling, "Evolutionary Divergence and Convergence in Proteins,"
Beyond Linus Pauling: Conformation dependence of ideal geometry in proteins
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Transcript of Beyond Linus Pauling: Conformation dependence of ideal geometry in proteins
![Page 1: Beyond Linus Pauling: Conformation dependence of ideal geometry in proteins](https://reader034.fdocuments.in/reader034/viewer/2022042716/55a6d6e01a28ab72298b4597/html5/thumbnails/1.jpg)
Beyond Linus Pauling: Conformation dependence
of ideal geometry in proteins
Donald S. BerkholzP. Andrew Karplus lab
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What is ideal geometry?
α α
R
R
NH2
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Where do you encounter ideal geometry?
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Where do you encounter ideal geometry?
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Where do you encounter ideal geometry?
![Page 6: Beyond Linus Pauling: Conformation dependence of ideal geometry in proteins](https://reader034.fdocuments.in/reader034/viewer/2022042716/55a6d6e01a28ab72298b4597/html5/thumbnails/6.jpg)
Where do you encounter ideal geometry?
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Where do you encounter ideal geometry?
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Ideal geometry paradigm is limited
N-Cα-C
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A new paradigm
N-Cα-C
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Why is this important?
RMSD(N-Cα-C)
Engh & Huber = 2.54°Conformation-Dependent Library = 1.65°
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Why is this important?
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Our approach
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Our approach
Protein Geometry Database
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Our approach
Protein Geometry Database
≤1.0 Å resolution
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Our approach
Protein Geometry Database
≤1.0 Å resolution Residues in PGD
19,516 (≤90% ID) 16,975 (≤25% ID)
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Our approach
Protein Geometry Database
≤1.0 Å resolution Residues in PGD
19,516 (≤90% ID) 16,975 (≤25% ID)
Conformation-Dependent Library
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What trends exist?N-Cα-Caverage
φ
ψ
107.5 114.0
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Averages known with high certaintyN-Cα-C
standarderror
ψ
φ0.1 1.1
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Dependent on local torsion angle
α α
R
R
NH2
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Dependent on local torsion angle
C-1-N-Cα
average
φ
ψ
α α
R
R
119.5 126.0
NH2
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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
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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
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Rationalizing φ = 40-90°
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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
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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
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New paradigm for peptide planarity
PDB: 2cws at 7.0σ
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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
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How could CDL improve refinement?
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How does CDL improve refinement?
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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°
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Conclusion
N-Cα-Caverage
φ
ψ
The old paradigm
110.5 110.5
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Conclusion
N-Cα-Caverage
ψ
φ
N-Cα-Caverage
φ
ψ
The old paradigm The new paradigm
107.5 114.0110.5 110.5
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Why is this important?
RMSD(N-Cα-C)
Engh & Huber = 2.39°Conformation-Dependent Library = 1.50°
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Why is this important?
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What is the impact of these variations?
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Approach to trend analysisN-Cα-Caverage
ψ
φ
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Approach to trend analysisN-Cα-Caverage
ψ
φ
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Peptide planarity is overexaggerated
Kang 2004