Carlos E. CrespoHernndez

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

• Carlos E. Crespo-Hernández
• Department of Chemistry
• Email carlos.crespo_at_case.edu
• Ohio Supercomputer Center
• Columbus, Ohio
• April 4, 2008

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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

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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 _at_ 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.
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Ultrafast Excited State Dynamics of Nucleic Acids
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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.
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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.
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Nucleic Acid Multimers Photophysics The Role of
Base Stacking and Base Pairing
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Effect of Base Stacking Interactions
Dinucleotides stack ? unstack Nucleotides
unstack
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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 Proceedings 2007, 963, 607.
R
AA AMP
?E 0.2 eV
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Reversible Redox Potentials of DNA Nucleosides
Crespo-Hernández, C.E. Close, M. D. Gorb, L.
Leszczynski J. Phys. Chem. B 2007, 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 ? Eox - Ered ? 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.
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Role of the Driving Force for Charge Separation
Crespo-Hernández, C.E. Cohen, B. Kohler, B.
Nature 2005, 436, 1141. Crespo-Hernández, C. E.
de la Harpe, K. Kohler, B. J. Am. Chem. Soc.
2008, submitted.
?G(GC) gt ?G(AT) gt ?G(IC)
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Excited State Dynamics and DNA Photochemistry Mak
ing Connections
Cadet, J. Vigny, P. In Bioorganic
Photochemistry Morrison, H., Ed. Wiley New
York, 1990 Vol.1, p 1.
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Thymine Dimerization in DNA is an Ultrafast
Reaction
Crespo-Hernández, C.E. Cohen, B. Kohler, B.
Nature 2005, 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. Science 2007, 315, 625.
Steady State IR
fs-Time-Resolved IR
fs-Transient Absorption
? 740 ? 12 fs
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Prediction of TltgtT 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.
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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.

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Conceptual Pump-Probe Transient Absorption
Experiment
probe
pump
DOD

0-
Delay / fs
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Femtosecond Pump-Probe Transient Absorption Setup
Beam Blocker
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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.
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Temperature Dependence of the Decays of PolyA and
AMP
Crespo-Hernández, C.E. Kohler, B. J. Phys. Chem.
B 2004, 108, 11182.
Excimer State is Localized between two Stacked
Bases.
PolyA
AMP