1. All-atom computer simulation of viruses in water
Introduction
Porcine circovirus 2 ( -2)PCV is an essential
problem for world economic today as the
morbidity of -2 infected piglets varies fromPCV
4% to 20%, while the mortality is as high as 90%.
The virus belongs to a class of nonenveloped
viruses (consisting of a protein shell and a orDNA
RNAmolecule inside) with icosahedral capsid (the
shell) and a single stranded . It is one of theDNA
smallest viruses in the world, with the capsid of
20.5 nm in diameter made by a single protein,
which atomistic structure is measured
experimentallybyX-raycrystallography.
However, crystallographic structure does not
reflect the in the cell. Firstly, inrealistic conditions
really the capsid is surrounded water, thisby
molecules guide conformational motions, which
cause all rearrangements of the protein . We,s
therefore, need to include water surrounding for
realistic results of the dynamics of virus molecules
in a cell. Secondly, X-ray crystallography cannot
see ssomepart ofstructure.
The method
The method Molecular Dynamics is based on solving Newton's second law
for every atom in the system
,F = ma
where is force exerted on the , is its mass and is its acceleration.F m aatom
Crystallographic structure of proteina single
Reconstruction the full capsid with missing sequences
Addition of water molecules
About 2 000 000 atoms in the system
Results
1. We have built an atomistic computer model for a
complete capsid of a virus, the model is
implementedinasmall‘personalsupercomputer’.
2. unknownWe have simulated 3 subunits without
parts after 30 ns in water and after 30 ns the
subunits were connected together. When we did
thesameinvacuum,theymovedapart.
3. We discovered that significant part of subunits
was missing from X-ray data. The cryo- imageEM
reconstruction showed that the location of the N
terminus, absent in the crystal structure is inside,
thecapsid.
4. theWe have checked influence of the 6 missing
partsonthe capsid.structureofthe
5. We have reconstructed the whole capsid without
andwithmissingparts.
Conclusions
simulated fferentWe have di parts of capsid and
demonstrated that ble .We havethey are sta in water
prepared the whole system for simulation. t isI a
very large system (about 2 000 000 atoms), ew are
currently performing the modelling using a high
performance computer .super inJapan
References
1. Reza Khayat, et al. 2011. The 2.3-Angstrom Structure of
Porcine Circovirus 2. J. Virol. 85: 7856–7862
2. Dmitry Nerukh and Sergey Karabasov.2013.
Water−Peptide Dynamics during Conformational Transitions.
J.Phys.Chem.Lett.4:815-819
3. R. A. Crowther, et al. 2003. Comparison of the Structures
of Three Circoviruses: Chicken Anemia Virus, Porcine
Circovirus Type 2, and Beak and Feather Disease Virus. J.
Virol. 77: 13036–13041.
4. Fan H., et al. 2007. Immunogenicity of empty capsids of
porcine circovius type 2 produced in insect cells. Vet Res
Commun.31:487-496.
5. Nawagitgul P., Morozov I., et.al. 2000.Open reading frame
2 of porcine circovirus type 2 encodes a major capsid protein.
J Gen Virol. 81:2281-2287.Acknowledgment
Thework issupportedbyTheRoyalSocietyofChemistry,SasakawaFoundation,Aston UniversityandRIKEN
ElviraTarasova , ShalishaPatrick DmitryNerukh
1 2 2
,
1
, , , ,Immanuel Kant Baltic Federal University 14 A, Nevskogo . 236041 Kaliningrad RussiaSTR
2
Systems Analytics InstituteResearch , Aston University, Birmingham, UK