1. No category

Wyzwania w procesie wysokoprzepustowego
modelowania istotnych funkcjonalnie
i terapeutycznie struktur 3D RNA
M. Popenda1, M. Szachniuk1,2, M. Antczak2 , T. Zok2 ,
T. Ratajczak2, P. Lukasiak1,2, K. J. Purzycka1,
K. Pachulska- Wieczorek1, M. Biesiada2, L. Blaszczyk2,
J. Blazewicz1,2 and R.W. Adamiak1,2*
1
Instytut Chemii Bioorganicznej PAN,
2 Politechnika Poznańska, Instytut Informatyki,
Europejskie Centrum Bioinformatyki i Genomiki
e-mail : [email protected]
PCSS_KDM_2015
PCSS_KDM_2015
Nucleic Acids Symposium Series No. 50, 67-68, OSAKA, 2006
2008 - RNA FRABASE concept
an engine with a database to search for the three-dimensional RNA fragments
PCSS_KDM_2015
http://rnafrabase.ibch.poznan.pl/
Stan na 1 maja 2015
M. Popenda, M. Blazewicz, M. Szachniuk and R.W. Adamiak.
RNA FRABASE version 1.0: an engine with a database to search for
the three-dimensional fragments within RNA structures.
Nucleic Acids Research 36, D386-D391 (2008)
M. Popenda, M. Szachniuk, M. Blazewicz, S. Wasik, E.K. Burke, J. Blazewicz and R.W. Adamiak.
RNA FRABASE 2.0: an advanced web-accessible database with the capacity
to search the three-dimensional fragments within RNA structures.
BMC Bioinformatics,, 11:231 (2010)
In view of the rapidly growing access to experimentally adjusted
large RNA secondary structures, their 3D structure
prediction is in great demand in the RNA research
community.
Only a few programs and web-accessible tools have been proposed
for automated prediction of the RNA tertiary structure.
They make use of:
coarse-grained and atomic-level molecular dynamics,
Sharma,S., Ding,F. and Dokholyan,N.V. (2008) Bioinformatics, 24, 1951-1952.
Jonikas,M.A., Radmer,R.J., Laederach,A., Das,R., Pearlman,S., Herschlag,D. and Altman,R.B. (2009) RNA, 15, 189-199.
Jonikas, M.A., Radmer, R.J. and Altman, R.B. (2009) Bioinformatics, 25, 3259-3266.
internal coordinate space dynamics,
Flores,S.C. and Altman,R.B. (2010). RNA, 16, 1769-1778.
Flores,S.C., Sherman,M.A., Bruns,C.M., Eastman,P. and Altman,R.B. (2011) IEEE/ACM Trans. Comput. Biol. Bioinform., 8, 1247-1257.
fragment assembly
Das,R., Karanicolas,J. and Baker,D. (2010) Nat Methods, 7, 291-294.
Parisien,M. and Major,F. (2008) Nature, 452, 51-55.
and comparative modelling using templates
Rother,M., Rother,K., Puton,T. and Bujnicki,J.M. (2011) Nucleic Acids Res., 39, 4007-4022.
PCSS_KDM_2015
None of them have accomplished
all the following criteria :
•
•
•
•
•
•
•
fidelity
prediction of large RNA structures
full automatization
very fast model building
large-scale modeling
user-friendly performance
web-accessible
PCSS_KDM_2015
RNAComposer
The concept
is founded on
the machine translation system
which is parallel to that employed in computational
linguistics
The translation engine operates on
the RNA FRABASE database
tailored to the dictionary
relating the RNA secondary structure
and tertiary structure elements.
.
PCSS_KDM_2015
RNAComposer
Since our report (Popenda, et al., 2012), the
volume of the dictionary has been substantially
enlarged and includes:
23,092 secondary structure elements (initially
14,464) and as much as 489,599 related 3D
structure elements (initially 190,928).
RNAComposer
SITES
http://rnacomposer.ibch.poznan.pl.
http://rnacomposer.cs.put.poznan.pl
RNAComposer
SITES
http://rnacomposer.ibch.poznan.pl.
http://rnacomposer.cs.put.poznan.pl
http://rnacomposer.ibch.poznan.pl
Stan :
1 maja 2015
Mirror site: rnacomposer.cs.put.poznan.pl
44073 visitors. Total over 104 thousands visitors
since 2012
14.5 sec.
HIV-2 SL1
High-throughput RNA 3D structure prediction
In the batch mode RNAComposer server can be loaded
with up to 100 RNA secondary structures.
100 secondary structures X 10 models requested = 1000 3D models
Moreover, when launching RNAComposer, user can enter own experimental
restraints, which makes the system very powerful.
Sequence
Secondary
structure prediction
Secondary structure
Major question:
how to access
an accurate
RNA secondary structure ?
RNAComposer
refined 3D structure
PCSS_KDM_2015
120-mer 5S rRNA H. Marismortui
in silico secondary structure prediction
UUAGGCGGCCACAGCGGUGGGGUUGCCUCCCGUACCCAUCCCGAACACGGAAGAUAAGCCCACCAGCGUUCCGGGGAGUACUGGAGUGCGCGAGCCUCUGGGAAACCCGGUUCGCCGCCACC
RNA FRABASE
...((((((....((((((((......((((((...(.....)...))))..))....)))))).))...(((((.....((((((.((....))))))))....)))))...))))))...
RNAStructure
...((((((....((((((((.(((.((.((((.............)))).)).))).)))))).))(..(((((.....((((((.((....))))))))....)))))..)))))))...
Contrafold
...((((((....((((((((.(((.((.((((.............)))).)).))).)))))).))(..(((((.....((((((.((....))))))))....)))))..)))))))...
RNAFold
...((((((....((((((((.(((.((.((((.............)))).)).))).)))))).))(..(((((.....(..(((.((....)))))..)....)))))..)))))))...
crystal structure
(1FFK)
as noted
in the RNA
FRABASE
database
RNAStructure
Contrafold
RNAfold
Matthews correlation
coefficient 87.40 %
Matthews correlation
coefficient 87.40 %
Matthews correlation
coefficient 84.07 %
120-mer
5S rRNA H. Marismortui
Dr Katarzyna Pachulska-Wieczorek
PCSS_KDM_2015
RNAComposer
5S rRNA H. Marismortui
tertiary structure
(10 models)
123-mer
r.m.s.d. [Å] global
r.m.s.d. [Å] 3-way junction
9.42
3.83
Superposition of the best 3D model (in purple)
generated from the secondary structure determined using RNAstructure & SHAPE
over the X-ray structure (PDB 1FFK) (in blue).
For reference, the best 3D model (in orange) generated from the ideal secondary structure
is presented.
r.m.s.d. [Å] global
r.m.s.d. [Å] 3-way junction
3.30
1.79
Bedlewo, 2011
3D RNA structure prediction
of the HIV-2 leader
PCSS_KDM_2015
HIV-2 leader RNA
secondary structure
HIV-2 leader RNA
3D structure
PCSS_KDM_2015
New HIV-2 leader RNA structure
(+1-560 )
captured as the loose dimer (1120-nt.)
Arrows point to
palindromes involved
in the kissing loop
formation (loose dimer)
PCSS_KDM_2015
RNAComposer – input
560-mer
PCSS_KDM_2015
Riboswiches
Purzycka. K.J., Popenda. M., Szachniuk. M., Antczak. M.,
Lukasiak. P., Blazewicz. J., Adamiak R.W.
Automated 3D RNA structure prediction using the RNAComposer
method for riboswitches.
Methods Enzymol. 2015;553:3-34. doi: 10.1016/bs.mie.2014.10.050.
Epub 2015 Feb 4. PMID: 25726459 (on-line December 2014)
Publications and associated serveres for RNA 3D structure
prediction and quality assessment
RNAlyzer--novel approach for quality analysis of RNA structural models.
Lukasiak P, Antczak M, Ratajczak T, Bujnicki JM, Szachniuk M, Adamiak RW,
Popenda M, Blazewicz J.
Nucleic Acids Res. 2013 Jul;41(12):5978-90. doi: 10.1093/nar/gkt318.
http://rnalyzer.cs.put.poznan.pl/
RNApdbee--a webserver to derive secondary structures from pdb files of knotted
and unknotted RNAs.
Antczak M, Zok T, Popenda M, Lukasiak P, Adamiak RW, Blazewicz J, Szachniuk M.
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W368-72. doi: 10.1093/nar/gku330.
http://rnapdbee.cs.put.poznan.pl/
Acknowledgements
R.W. Adamiak, NCN MAESTRO 3:
„Automatyczne, wysokoprzepustowe
modelowanie struktur przestrzennych RNA”
POWIEW
Centrum Kompetencji PCSS
Dr Norbert Meyer, Dr Marcin Lawenda
PCSS_KDM_2015