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Excess Energy Flow in DNA: Bench and Computer Experiments Working in Unison

Excess Energy Flow in DNA: Bench and Computer Experiments Working in Unison. Carlos E. Crespo-Hernández Department of Chemistry Email: carlos.crespo@case.edu Ohio Supercomputer Center Columbus, Ohio April 4, 2008. Acknowledgement. Prof. Bern Kohler and Group Members

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Excess Energy Flow in DNA: Bench and Computer Experiments Working in Unison

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  1. Excess Energy Flow in DNA: Bench and Computer Experiments Working in Unison Carlos E. Crespo-Hernández Department of Chemistry Email: carlos.crespo@case.edu Ohio Supercomputer Center Columbus, Ohio April 4, 2008

  2. Acknowledgement Prof. Bern Kohler and Group Members National Institute of Health (R01-GM64563) Prof. Terry Gustafson and the Center for Chemical and Biophysical Dynamics, The Ohio State University Ohio Supercomputer Center Case Western Reserve University NSF-ACES Program and NSF-MRI Grant CHE0443570

  3. Ohio Supercomputer Center Allocations (since 2005) • Software • Gaussian 03: 2CPUs in parallel, 10-12 hrs, ~ 150-200 RUs • GROMACS: 4 CPUs in parallel (scaling: 99%), 150 ns trajectories @ 0.767 hrs/ns, • ~ 50 RUs + ~ 100 RUs for free energy simulations: ~100 RUs • Storage Needs • For the systems and trajectories we are currently running we use ~ 200MB/ns or ~100GB of storage space (before compressed) + scratch space. • Future larger model systems would necessitate larger scale simulations: 8CPus in parallel (scaling: ~81%) at 2.4 hrs/ns. Publications 1. Close, M. D.; Crespo-Hernández, C. E.; Gorb, L.; Leszczynski, J. J. Phys. Chem. A 2005, 109, 9279. 2. Close, M. D.; Crespo-Hernández, C. E.; Gorb, L.; Leszczynski, J. J. Phys. Chem. A 2006, 110, 7485. 3. Crespo-Hernández, C. E.; Close, M. D.; Gorb, L.; Leszczynski, J. J. Phys. Chem. B 2007, 111, 5386. 4. Crespo-Hernández, C. E.; Marai, C. N. J. AIP Conference Proceedings 2007, 963, 607. 5. Law, Y. K.; Azadi, J.; Crespo-Hernández, C. E.; Olmon, E.; Kohler, B. Biophysical J.2008, in press. 6. Close, M. D.; Crespo-Hernández, C. E.; Gorb, L.; Leszczynski, J. J. Phys. Chem. A 2008, in press. 7. Crespo-Hernández, C. E.; Burdzinski, G.; Arce, R. J. Phys. Chem. A 2008, submitted.

  4. … … … Ultrafast ExcitedState Dynamics of Nucleic Acids

  5. S1 Lifetimes for Nucleosides DNA RNA Pecourt, J.-M.L.; Peon, J.; Kohler, B. J. Am. Chem. Soc.2001, 123, 10370. Crespo-Hernández, C.E.; Cohen, B.; Hare, P.; Kohler, B. Chem. Rev., 2004, 104, 1977. Cohen, B.; Crespo-Hernández, C.E.; Kohler, B. J. Chem. Soc.,Faraday Discuss.2004, 127, 137.

  6. Role of Conical Intersections in the Radiationless Decay of DNA Monomers: Cytosine Conical intersections are a likely mechanism for the ultrafast lifetimes of cytosine and the other DNA bases. Pecourt, J.-M.L.; Peon, J.; Kohler, B. J. Am. Chem. Soc.2001, 123, 10370. Merchán, M.; Serrano-Andrés, L. J. Am. Chem. Soc., 2003, 125, 8108.

  7. Nucleic Acid Multimers Photophysics: The Role of Base Stacking and Base Pairing

  8. TD-DFT/B3LYP/6-311G(d,p) L+1 L H H-1 S2 S1 263.6 nm,0.0298H -> L+1 60% H-1 -> L 40% 275.6 nm,0.0266H -> L 78% H-1 -> L+1 22% S0 Effect of Base Stacking Interactions Dinucleotides: stack↔unstack Nucleotides: unstack

  9. A-AA R = 3 Å Ade R = 4 Å R = 5 Å R = 6 Å HOMO LUMO A-AA6 Electronic Coupling versus Interchromophoric Distance TD-DFT/B3LYP/6-311G(d,p) Calculations of A-Form ApA Crespo-Hernández, C.E.; Marai, C.N.J. AIP Conference Proceedings2007, 963, 607. R AA AMP E= 0.2 eV

  10. Reversible Redox Potentials of DNA Nucleosides Crespo-Hernández, C.E.; Close, M. D.; Gorb, L.; Leszczynski J. Phys. Chem. B2007, 111, 5386.

  11. Charge Transfer Character of the Excimer/Exciplex Tomohisa, T.; Su, C.; de la Harpe, K; Crespo-Hernández, C.E.; Kohler, B. Proc. Natl. Acad. Sci. USA 2008, accepted. G°  E°ox - E°red  IP - EA The decay rates of the long-lived states increase with increasing driving force for charge recombination as expected in the Marcus inverted region.

  12. Role of the Driving Force for Charge Separation • Crespo-Hernández, C.E.; Cohen, B.; Kohler, B. Nature2005, 436, 1141. • Crespo-Hernández, C. E.; de la Harpe, K.; Kohler, B. J. Am. Chem. Soc.2008, submitted. d(AT)9•d(AT)9 d(GC)9•d(GC)9 d(IC)9•d(IC)9 ΔG(GC) >ΔG(AT) >ΔG(IC)

  13. Singlet or triplet state? UV Formation time scale? T<>T photodimers account for ~90% of DNA Damage* Excited State Dynamics and DNA Photochemistry: Making Connections * Cadet, J.; Vigny, P. In Bioorganic Photochemistry; Morrison, H., Ed.; Wiley: New York, 1990; Vol.1, p 1.

  14. Thymine Dimerization in DNA is an Ultrafast Reaction • Crespo-Hernández, C.E.; Cohen, B.; Kohler, B. Nature2005, 436, 1141. • Schreier, W.J.; Schrader, T.E.; Koller, F.O.; Gilch, P.; Crespo-Hernández, C.E.; Swaminathan, V.N.; Carell, T.; Zinth, W.; Kohler, B. Science2007, 315, 625. Steady State IR fs-Time-Resolved IR Time / ps fs-Transient Absorption  = 740  12 fs

  15. Prediction of T<>T Yields from MD Simulations Law, Y.K.; Azadi, J.; Crespo-Hernández, C.E.; Cohen, B.; Kohler, B. Biophysical J. 2008, in press. Water/EtOH YieldExp. YieldMD (x 102) ----------------------------------------------------------- 0% 1.6 ± 0.3 1.7 40% 1.1 ± 0.1 1.3 50% 0.7 ± 0.2 0.6 Hypothesis: ground-state conformation at the instant when dTpT absorbs light controls the photodimer yield.

  16. Conclusions Our combined experimental and computational studies have shown: • Base stacking controls the excited state dynamics on single and double stranded DNA, forming new long-lived singlet excited states not observed in the monomers. • The driving force for charge separation and charge recombination in the DNA base stacks modulates the dynamics of the long-lived singlet state. • The major DNA photoproduct, the thymine photodimer, is formed in less than 1ps in thymine-thymine base stacks and the ground state conformation controls whether the photodimer reaction takes place or not. • Theoretical calculations have been essential for the visualization of the molecular processes and the elucidation of specific mechanisms of nonradiative deactivation of the excited states in DNA.

  17. … Sn probe … S1 A Energy pump S0 … … t < 0 t = 0 t = t1 t = tn probe delay “initiation” Sn 6 eV Time / fs S1 4.2 eV kr knr S0 0 eV probe600 nm pump267 nm Conceptual Pump-Probe Transient Absorption Experiment probe pump DOD 0- Delay / fs

  18. Femtosecond Pump-Probe Transient Absorption Setup Mira, Evolution, Legend OPA; 230-1300 nm 2.9 W , 800 nm, 35 fs mm BBO Delay Stage 400 nm Water Cell mm BBO 1cm Computer Controlled Wave Plate 267 nm WLC; 350-900 nm Prism-Compressor Optical Chopper Lockin Amplifier Polarizer 1mm F l o w C el l Monochrometer PD/PMT Beam Blocker

  19. Ultrafast Deactivation Channel for Thymine Dimerization Boggio-Pasqua, M.; Groenhof, G.; Schäfer, L.V.; Grubmüller, H.; Robb, M.A. J. Am. Chem. Soc.2007, 129, 10996.

  20. Temperature Dependence of the Decays of PolyA and AMP Crespo-Hernández, C.E.; Kohler, B. J. Phys. Chem. B2004, 108, 11182. Excimer State is Localized between two Stacked Bases. PolyA AMP

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