The role of geometry in translocation processes of and on nucleic acids [Elektronische Ressource] : ribosomal frameshift and dynamic target search / Thomas Schötz. Betreuer: Ulrich Gerland

Thomas Schötz

Sujets

• Physik

Informations

• Publié par: ludwig-maximilians-universitat_munchen
• Publié le: 01 janvier 2011
• Nombre de lectures: 7
• Langue: English
• Poids de l'ouvrage: 17 Mo

Extrait

The role of geometry in translocation processes
of and on nucleic acids
ribosomal frameshift and dynamic target search
Thomas Schötz
th
Munich, November 18 , 2010
The role of geometry in translocation processes
of and on nucleic acids
ribosomal frameshift and dynamic target search
Thomas Schötz
Dissertation der Fakultät für Physik
der
Ludwig-Maximilians-Universität
München
vorgelegt von
Thomas Schötz
aus Straubing
München, 18. November 20101. Gutachter: Prof. Dr. U. Gerland
2. Gutachter: Prof. Dr. H. Stark
Tag der mündlichen Prüfung: 26. Januar 2011“Loppu hyvin, kaikki hyvi” n
(Finnish proverb)Contents
List of figures ..............................v.ii.........................................................
Zusammenfassung ............................xi.....................................................
Abstract .................................xii.i..............................................................
1 Introduction ..............................1...........................................................
1.1 Translocation processes occurring within the central dogma........1...............
1.2 Translocation of RNA hairpins and pseudoknots through ribosome.s ...2......
1.3 Translocation of proteins on DNA: A target search proces.s ........5.................
2 RNA folding, deformation and pore translocation..........9..................
2.1 Model......................................9...........................................................................
2.1.1 Geometry ..................................9...................................................................
2.1.2 Dynamic.s................................1.2................................................................
2.2 Folding of RNA................................1.6..............................................................
2.3 Deformation of folded RNA ..........................21..................................................
2.3.1 Stretching a hairp.in..........................2.1.....................................................
2.3.2 Bending a hairp.in............................25........................................................
2.3.3 Drilling a hairp.in............................30........................................................
2.4 Quantitative calibration of the RNA model.................32.................................
2.5 Translocation of hairpins and pseudoknots.................3.8 ................................
2.5.1 Structure of hairpins and pseudoknots.................3.9................................
2.5.2 Characterization of the system using the hairpin paradig.m.....4.1 .........
2.5.3 Hairpin translocation versus pseudoknot translocati.on.......5.4..............
2.6 Conclusion...................................7.1 ...................................................................
3 Protein target search on DNA ....................7.5 ....................................
3.1 Model.....................................7.5.........................................................................
3.2 Protein transport simulations on the DNA ch.ai.n............7.8.........................
3.2.1 Observation.s..............................7.8.............................................................
3.2.2 Theoretical explanation of the observations ...............80...........................
3.3 Protein transport and correlation.s.....................81..........................................vi Contents
3.3.1 Lévy-type superdiffusion vs. quasi-diffusion and the role of cor­ rela
tions.......................................8.1 ............................................................................
3.3.2 Spatial vs. temporal correlation.s....................82.......................................
3.3.3 Geometric properties of static intersegment link patterns .......83............
3.4 Islan.ds....................................9.0.......................................................................
3.4.1 Definition.................................9.2................................................................
3.4.2 Statistical properties of RW islands...................9.3...................................
3.5 Toy model...................................9.9....................................................................
3.5.1 Transport on the hopping environment: Simulation.s ........10.1...............
3.5.2 Transport on the hopping environment: Theory ............10.2.....................
3.5.3 Transport on the leaping environment: Theory ............1.05......................
3.5.4 Transport on the leaping environment: Simulation.s........1.07................
3.5.5 Parameter space diagram.s......................1.08............................................
3.6 Conclusion..................................1.10..................................................................
Appendix A: Brownian dynamics algorithm.............1.15........................
Appendix B: Fractional calculus and CTRWs ............1.17......................
B.1. Normal diffus.ion..............................118...........................................................
B.2. Long rests: subdiffu.si.on.........................11.8 ...................................................
B.3. Long jumps: Lévy fl.ig.ht.s.......................1.19..................................................
B.4. Competition between long rests and long jump.s.............119.........................
B.5. Competition in inter-correlated CTRWs ..................12.0.................................
Bibliography ..............................1.21.........................................................
Danksagung..............................1.29..........................................................List of figures
Fig. 1.1 Central Dogma of biology page 1
Fig. 1.2 HIV, ribosomes and ribosomal frameshift page 3
Fig. 1.3 Transcription factors and their binding sites on DNA page 6
Fig. 2.1 Coarse-graining an RNA base-pair page 9
Fig. 2.2 Comparing the space of base-pairing and 3D space page 11
Fig. 2.3 Vectors and angles in the RNA model page 11
Fig. 2.4 RNA chain in pore potential page 13
Fig. 2.5 Binding weights page 14
Fig. 2.6 Binding predicate function page 16
Fig. 2.7 Base compatibility in the Watson-Crick model and in the Go model page 17
Fig. 2.8 Lennard-Jones energy contributions in several binding models page 18
Fig. 2.9 Process of hairpin folding page 19
Fig. 2.10 Distribution of the base-pair number at several temperatures page 20
Fig. 2.11 Regimes of axial stem deformation for vanishing torsion energy page 23
Fig. 2.12 Force extension relation for a folded hairpin when stretched axially page 25
Fig. 2.13 Geometry of the bending experiment page 26
Fig. 2.14 Force elongation diagram for large elongations page 27
Fig. 2.15 Force elongation diagram for small elongations page 27
Fig. 2.16 Collapsing curves due to identical slopes for low temperatures page 28
Fig. 2.17 Slopes decreasing with increasing temperature for high temperatures page 28
Fig. 2.18 Slopes are sensitive of the bending energy parameter for low temperatures page 28
Fig. 2.19 Slopes are insensitive of the bending energy parameter for high temperatures page 28
Fig. 2.20 Slope vs. temperature for several bending energy parameters (low temp.) page 29
Fig. 2.21 Slope vs. temperature for several bending energy parameters (all temp.) page 29
Fig. 2.22 Folding probability vs. temperature for several bending energy parameters page 29
Fig. 2.23 Occurrence of backbone deformation depends on bending direction page 30
Fig. 2.24 Effective bending stiffness linear if torsion potential vanishes page 30
Fig. 2.25 Hairpin torsion experiment for zero and positive total drill angles page 31
Fig. 2.26 Drill angles and torque for elementary cells and the whole hairpin stem page 31viii List of figures
Fig. 2.27 Axial torque vs. time for different total drill angles page 32
Fig. 2.28 Equilibrium axial torque vs. total drill angle, parametrized by temperature page 32
Fig. 2.29 Geometric parameters of RNA page 33
Fig. 2.30 Torsional modulus vs. torsion and bending energy parameter page 35
Fig. 2.31 Persistence length vs. torsion and bending energy parameter page 35
Fig. 2.32 Stem integrity vs. torsion and bending energy parameter page 35
Fig. 2.33 Energy parameters providing correct torsional modulus and persistence length page 36
Fig. 2.34 Controlling the base-pair stabilizing side-effect of the angular potentials page 37
Fig. 2.35 Helical and tilted initial geometry of a hairpin in front of a pore page 40
Fig. 2.36 Helical and tilted initial geometry of a pseudoknot in front of a pore page 40
Fig. 2.37 Parameter space regimes of chain passing, chain pausing and chain rejection page 42
Fig. 2.38 Translocation pauses (stem neither opens nor is deformed sufficiently) page 43
Fig. 2.39 Double-stranded translocation (stem closed but deformed sufficiently) page 43
Fig. 2.40 Decision tree: rejection, pausing, double and single stranded translocation page 45
Fig. 2.41 Isotherm intersecting the coexistence lines in parameter space of chain behavior page 46
Fig. 2.42 Constant low translocation rate for short times: regime of stem unzipping page 47
Fig. 2.43 Constant high translocation rate for sh