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.)

1

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.

2

Explicit ImplicitCoulomb: 83 kcal/mol/ 83 kcal/mol/ Solvation: -32 kcal/mol/ -30 kcal/mol/Total Elec: 51 kcal/mol/ 53 kcal/mol/

NaCl

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

3

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).

4

Parallel Computation Explicit GB (Naive) GB (NAMD)

5

Cores Cores Cores

Same #pairs/atomSame #atoms/cell

GOOD

Different #pairs/atomDifferent #atoms/cell

BAD

Excellent Parallel Performance

130,000

149,000

27,600

29,500

2,016

2,412

# Atoms

NAMD

Traditional

6

42 ns/day25 ns/day

2W49

1IR2

3EZQ

3AK8

2KKW

2W5U

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]

7

D. Sitkoff, K. Sharp, and B. Honig. Accurate calculation of hydration free energies using macroscopic solvent models. J. Phys. Chem. 98:19781988 (1994).

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).

8

Needs compensation

HybridGB / SA

onGPU / CPU

9

Total Valid Fract

GB 1.7x108 6.5x106 3%

SA 2.3x1012 5.2x106 0.0002%

group

grou

p

group

13,340 atom1GPB

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

10

Allow switching bydividing SA calculationinto small work units.

Solution

HybridGB/SA

Execution

11

Excellent Efficiency

time

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

Molecular Dynamics Flexible Fitting 13

Initial CrystalStructurePDB 2EZMFitted

Structure

Simulated cryo-EM Mapfrom PDB 3EZM

Cyanovirin-N1,500 atoms40 ns/day on GPU

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.