generalized born implicit solvent
DESCRIPTION
David HardyTRANSCRIPT
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Generalized Born Implicit SolventAlgorithm in NAMD
David Hardyhttp://www.ks.uiuc.edu/Research/gpu/NAIS: State-of-the-Art Algorithms for Molecular Dynamics
(Presenting the work of David Tanner.)
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Generalized Born Implicit Solvent Benefits
instantaneous relaxation of waterlow viscosityincreased diffusionincreased flexibility
Caveatsdescribes bulk water onlyno hydrogen bonding
ImplicitSolvent
ExplicitSolvent
Fewer atoms should be faster.
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Explicit ImplicitCoulomb: 83 kcal/mol/ 83 kcal/mol/ Solvation: -32 kcal/mol/ -30 kcal/mol/Total Elec: 51 kcal/mol/ 53 kcal/mol/
NaCl
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Born Radius
Each atom exposed to other atomsand solvent
Surrounded by:Solvent (polar)
=80Protein (nonpolar)
=1
Many Neighbors=1low screeninglarge Born radius
Few Neighbors=80high screeningsmall Born radius
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GBIS is Expensive (7X)Generalized Born Implicit SolventCoulomb
Onufriev, Bashford and Case. Exploring Protein Native States and Large-Scale Conformational Changes With a Modified Generalized Born Model. Proteins: Struct., Funct., Bioinf. 55:383394 (2004).
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Parallel Computation Explicit GB (Naive) GB (NAMD)
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Cores Cores Cores
Same #pairs/atomSame #atoms/cell
GOOD
Different #pairs/atomDifferent #atoms/cell
BAD
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Excellent Parallel Performance
130,000
149,000
27,600
29,500
2,016
2,412
# Atoms
NAMD
Traditional
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42 ns/day25 ns/day
2W49
1IR2
3EZQ
3AK8
2KKW
2W5U
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GB / SA Implicit SolventGeneralized Born Solvent-Accessible Surface Area
Hydrophilic Free Energy of Solvationpolar effectCoulomb interactions of waterscreens electrostatics
Hydrophobic Free Energy of Solvationnonpolar effectvan der Waals interaction of watersurface tension constricts protein
E = Surf_Tension * Surf_Area
[kcal/mol/2] * [2]
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D. Sitkoff, K. Sharp, and B. Honig. Accurate calculation of hydration free energies using macroscopic solvent models. J. Phys. Chem. 98:19781988 (1994).
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Linear Combination of Pairwise Overlaps
RjRi
rij
duplicateoverlaps
J. Weiser et al. Approximate atomic surfaces from linear combinations of pairwise overlaps (LCPO). J. Comp. Chem. 20:217230 (1998).
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Needs compensation
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HybridGB / SA
onGPU / CPU
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Total Valid Fract
GB 1.7x108 6.5x106 3%
SA 2.3x1012 5.2x106 0.0002%
group
grou
p
group
13,340 atom1GPB
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Hybrid CalculationThe GPU requires a host CPU to copy data and submit work.
copy data to GPUinitialize work on GPU
SAreceive data from GPUperform GB reductioncopy data to GPUinitialize work on GPU
SAreceive data from GPU...
Time
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Allow switching bydividing SA calculationinto small work units.
Solution
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HybridGB/SA
Execution
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Excellent Efficiency
time
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Performancein vacuo
GB
GB/SA 12
74,930 (1IR2): 10 ps/day (1c) 410 ps/day (1g1c) = 40X13,340 (1GPB): 0.33 ns/day (1c) 9.4 ns/day (1g16c) = 28X
12 nm
1IR2
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Molecular Dynamics Flexible Fitting 13
Initial CrystalStructurePDB 2EZMFitted
Structure
Simulated cryo-EM Mapfrom PDB 3EZM
Cyanovirin-N1,500 atoms40 ns/day on GPU
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14MDFF of Ribosome
fitting classical-state crystal structure50S (2I2V) is 3.2 resolution30S (2I2U) is 3.2 resolution
into ratcheted-state cryo-EM density map8.9 resolution
37 ns/day5.2 ns/day
3.6 ns/day
1000 proc.