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Hydrogen bonds in Rosetta:a phenomonological study
Jack SnoeyinkDept. of Computer ScienceUNC Chapel Hill
Key points
My biases Hydrogen bonds in Rosetta
Structure-derived potential of KMB03 Existing definition/scoring Comparing natives & decoys Proposed recategorization
Bad smells in code Open questions
Phenomenology defined:
Movement originated by E. Husserl in 1905
A philosophy based on the premise that reality consists of objects and events as they are perceived or understood in human consciousness and not of anything independent of human consciousness.
Phenomenology defined:
Movement originated by E. Husserl in 1905
A philosophy based on the premise that reality consists of objects and events as they are perceived or understood in human consciousness and not of anything independent of human consciousness.
Structure-derived potential KMB03
Energy from observed structures: distance dependence for helix
0
200
400
600
800
1000
1200
1400
1.45
1.55
1.65
1.75
1.85
1.95
2.05
2.15
2.25
2.35
2.45
2.55
2.65
2.75
2.85
Structure-derived potential KMB03
Energy from observed structures: statistically derived energies…
-2
-1
0
1
2
3
1.45
1.55
1.65
1.75
1.85
1.95
2.05
2.15
2.25
2.35
2.45
2.55
2.65
2.75
2.85
Three tasks in Hbond scoring
Identify pairs of atoms that Hbond
Classify Hbond types
Evaluate energies for Hbonds
Rosetta++ mixes these tasks together…
Three tasks in Hbond scoring
As described in KMB03 Identify pairs of atoms that Hbond
Params: AH distance, , Classify Hbond types
BB: helix, strand, other; AH distance SS,BS,SB: acceptor hybridization; AH dist
Evaluate energies for Hbonds Sum three potentials on AH distance, , , Amino acid weights Residue neighbors for donor/acceptor
Three tasks in Hbond scoring
As implemented in Rosetta++ Identify pairs of atoms that Hbond
Params: AH distance, , Classify Hbond types
BB: separation short |sep|≤4; long range SS,BS,SB: acceptor hybridization; AH dist
Evaluate energies for Hbonds Sum three potentials on AH distance, , Amino acid weights OR
Residue neighbors for donor/acceptor
SS bonds: native & decoy
sp2
ED
QN
bb
sp3
TS
Y
ring
H
dist Natives: Dunbrack set of 3157 structures
some pdb errors Decoys: Best 20 for each of Rhiju’s ab
initio runs on 62 structures small proteins few parallel beta strands
Rosetta places Hs & determines Hbonds Filter energies < -0.1 Visualization: Tufte’s small multiples Normalization
Express counts as fraction of all Hbonds to support comparison of colors in each plot
Plot with common x axis; scale y to max height
Number (and percentage) of bonds under the existing classification
Counts Percentage
Native Decoys Native Decoys
BB
Helix (+/-4) 185,204 38,128 32.28 50.66
Turn (+/-3) 79,110 8,983 13.79 11.94
Other 150,945 19,459 26.31 25.85
S
sp2 ED QB bb 132,522 6,448 23.10 8.57
sp3 TS Y 23,641 2,062 4.12 2.74
ring H 2,325 184 0.41 0.24
TOTALS 573,747 75,264 100.00 100.00
Observations
Rosetta does well at optimizing what it is told.
Decoy distributions are more sharply peaked than natives.
Relax preserves more non-helix bonds than ab initio, but produces same shapes for param distrib’ns. To test changes, it suffices to run relax.
Three tasks in Hbond scoring
Proposed changes Identify pairs of atoms that Hbond
Params: AH distance, , Classify Hbond types
BB: finer separation (Beta?) SS,BS,SB: finer don/acc chemical types
Evaluate energies for Hbonds: options1. Sum three potentials on AH distance, , 2. Potential on three variables AH distance, , 3. Add neighbors4. Add a torsion as 4th or 5th variable Weights for tuning different terms
Parallel vs Anti-parallel beta
The standard figures are misleading;
parallel and anti-parallel form similar distance, , distributions.
Refactoring Hbonds
Recategorizing should eliminate long-range & short-range Hbonds;which are used outside of hbonds.cc – they shouldn’t need to be.
Duplicated code in minimizers needs to be brought back into hbonds.cc