University	  of	  Tsukuba	  	  | Center	  for	  Computational	  Sciences

Computational	  Elucidations	  for	  Biomolecules
QM/MM	  and	  MD	  simulations	  using	  supercomputers
In biology, there still remain numerous unsolved issues regarding to the actual structures, functions and reaction
mechanisms for biomolecules, though they are critically important for all living organisms. In order to answer suchchallenging questions, we have been using highly accurate physical simulations based on quantum mechanics / molecularmechanics (QM/MM) and molecular dynamics (MD). In both methods, fundamental physical equations are numericallysolved by computers.
(a)

(b)

QM	  region
resamplingcriteria

CaMn4O5 cluster
2H2O

O2

4H+Fig. 1: (a) QM/MM model of oxygen evolving complex in photosystem II. Key intermediate states in the catalytic reaction “2H2O + 4hv -­‐>
4H++4e–+O2” have been investigated using the large model. [M. Shoji et al., Catal. Soc. Technol., 3, 1831 (2013).](b) Effective conformational sampling of MD simulations: Parallel Cascade Selection MD (PaCS-­‐MD). To promote the conformational transition,
the following cycle is repeated in PaCS-­‐MD; (I) Selections of initial seeds (structures) that have high potential to transit. (II) The conformational
resampling through restarting multiple MD simulations from the selected initial seeds. [R. Harada et al., J. Chem. Phys. 139 035103 (2013)]

GPU-­‐accelerated	  Molecular	  Orbital	  Calculation
Large-­‐scale ab initio molecular orbital calculation is a target application in quantum chemistry for HPC computer systems,
and the fragment molecular orbital (FMO) method is one of such application because it is designed for parallel computer.
We have developed GPU-­‐accelerated FMO calculation program with CUDA, and obtained 3.8x speedups from CPU on-­‐the-­‐fly
FMO calculation of 1,961 atomic protein. [H. Umeda et al., IPSJ Transactions on Advanced Computing Systems 6, 4, (2013) 26-­‐37. H. Umeda et al., SC15 poster (2015).]
(a)

(b)

Divides	  into	  fragments

SCF	  calc.	  for	  each	  fragment	  	  with	  ESP	  (SCC)

Application#Atoms#Nodes (#GPU)
SCC
Dimer SCF
ES Dimer
Total

(c)

Dimer	  SCF	  or	  ES-­‐Dimer	  calc.	  
for	  each	  fragment-­‐pair

Lysozyme
1,961
8 (32)
8 (0)3,071 s828 s6,246 s 1,675 s
407 s
78 s
9,770 s 2,597 s

3.7x
3.7x
5.2x
3.8x

HA3
23,46064 (256)
0.52 hr0.90 hr0.45 hr
1.97 hr

Influenza	  HA3	  protein(23,460	  atoms,	  721	  fragments)

2 Hours for FMO
calculation with 256 GPUs

Fig. 2: (a) FMO calculation scheme, where large molecule is divided into many small fragments. Total molecular properties are reconstructed from theself consistent field (SCF) calculations of fragments and fragment-­‐pairs with SCC (self-­‐consistent-­‐charge)-­‐condition-­‐satisfied electrostatic potential (ESP).
(b) Performance of GPU-­‐accelerated FMO calculations. GPU-­‐accelerated FMO-­‐HF/6-­‐31G(d) calculation of lysozyme with HA-­‐PACS base cluster shows
3.8x speedups.
(c) As large-­‐scale MO application, FMO-­‐HF/6-­‐31G(d) calculation of Influenza HA3 protein is successfully performed with 256 GPUs within two hours.

contact	  address:	  shigeta@ccs.tsukuba.ac.jp

http://www.ccs.tsukuba.ac.jp/