BarMap & SundialsWrapper

Transcription

1 BarMap & SundialsWrapper advanced RN folding kinetics Stefan Badelt Institute for Theoretical hemistry Theoretical Biochemistry roup February 17, 215 1

2 Outline BarMap.pm & SundialsWrapper.pm Two libraries... BarMap.pm interface to RN folding kinetics on static landscapes kinetics on time-varying energy landscapes SundialsWrapper.pm solving arbitrary RNs using the Sundials VODE -library BarMap.pm RNsubopt barriers treekin SEQENE e+6 1e+8 Time/a.u. Sundials VODE SundialsWrapper.pm e+6 1e+8 Time/a.u. 2

3 Outline BarMap.pm & SundialsWrapper.pm Two libraries... BarMap.pm interface to RN folding kinetics on static landscapes kinetics on time-varying energy landscapes SundialsWrapper.pm solving arbitrary RNs using the Sundials VODE -library...and many tools: BarMapSimulator.pl simulations on time-varying energy landscapes interkin.pl kinetics of (multiple) pairwise interacting RNs transkin.pl co-transcriptional folding of long RN molecules... 2

4 BarMap library BarMapSimulator.pl kinetics on time-varying energy landscapes SEQENE RNsubopt barriers BarMap.pm occupancy 1,8,6,4 treekin SEQENE, time Ivo L. Hofacker, hristoph Flamm, hristian Heine, Michael T. Wolfinger, erik Scheuermann, and Peter F. Stadler, BarMap: RN folding on dynamic energy landscapes, RN, (21) 3

5 BarMap and co-transcriptional folding 1,8,6,4,

6 BarMap and co-transcriptional folding 1 BarMap Simulation co-transcriptional folding,8 Population Density,6,4,2,1,2,3,4,5,6,7,8,9 1 1,1 1,2 1,3 Time [seconds] 4

7 BarMap including ligand interactions BarMap Simulation, B X 1 (no Theophylline) Structure Structure B Structure X Population Density 2.91 x Population Density Time [seconds] BarMap Simulation (+ Theophylline) 1 Structure Structure B Structure X x Time [seconds] Stefan Badelt, Stefan Hammer, hristoph Flamm, and Ivo L. Hofacker, Thermodynamic and kinetic folding of riboswitches, Methods in Enzymology, Elsevier, in press. Manja Wachsmuth, Sven Findeiß, Nadine Weissheimer, Peter F. Stadler and Mario Mörl, De novo design of a synthetic riboswitch that regultes termination transcription, NR, (212) 5

8 SundialsWrapper libary SundialsWrapper.pm solving arbitrary RNs using the Sundials VODE -library B.m RNsubopt barriers treekin SEQENE e+6 1e+8 Time/a.u. t t t m lar tics t a t m lar t m lar Sundi rapper.m Sundials VODE e+6 1e+8 Time/a.u. 6

9 SundialsWrapper libary SundialsWrapper.pm solving arbitrary RNs using the Sundials VODE -library 7"8"656$ RNsubopt barriers treekin SEQENE e+6 1e+8 Time/a.u.!"# "$%&'(lar &%'"& tics )*+,- #&%/ ""1 )23# "$%&'(lar $%&'(lar Sundi"&#4rapper56$ Sundials VODE e+6 1e+8 Time/a.u. 6

10 interkin.pl kinetics of interacting molecules compute intra-molecular rates for each monomer compute intra-molecular rates for all interacting dimers compute transition rates between monomers and dimers +B <=> B barr barriers --,B,B barriers -- B 7

11 RNfolding of interacting molecules,1 +B <=> B population density [mol/l],8,6,4,2 1 1e+5 1e+1 arbitrary time units 8

12 RNfolding of interacting molecules,1 + <=>, B+B <=> BB, +B <=> B population density [mol/l],8,6,4,2 1 1e+5 1e+1 arbitrary time units 8

13 transkin.pl co-transcriptional folding of large RNs S = () for each RNsequence of the growing chain 1 s = MFE-structure of current sequence, unless s S { S = S +s compute refolding rates to all currently populated structures } 2 simulate RN using SundialsWrapper 9

14 transkin.pl co-transcriptional folding of large RNs,1,1 1 1 time [s],2,4,6,8 occupancy cotranscriptional folding (843nt) 1 9

15 thanks to This work Ivo L. Hofacker hristoph Flamm... and the whole TBI group Design Projects: XOR riboswitches Peter F. Stadler Mario Mörl Regula rreger esine Domin RNprions Sabine Müller Sonja Petkovic co-transc. folding of 3 TRs ndrea Tanzer Michael T. Wolfinger Michael Jantsch Konstantin Licht Mansoureh Tajaddod The research was funded by the ustrian Science Fund (FWF): W127-B9, I67-B11 1