Slajd 1 - Konferencja użytkowników KDM
Transcription
Slajd 1 - Konferencja użytkowników KDM
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 : adamiakr@ibch.poznan.pl 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