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Transcript of Carlos E. Crespo-Hernández Department of Chemistry Email: [email protected] Ohio Supercomputer...
Carlos E. Crespo-HernándezDepartment of Chemistry
Email: [email protected]
Ohio Supercomputer CenterColumbus, Ohio
April 4, 2008
Excess Energy Flow in DNA: Bench and Computer Experiments
Working in Unison
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
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.
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
Ultrafast Excited State Dynamics of Nucleic Acids
…
…
…
S1 Lifetimes for Nucleosides
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.
1086420
AS /
10
4
2.01.00.0
Time / ps
Urd: = 230 ± 30 fs
6
4
2
0
AS /
104
5.02.50.0
Time / ps
Cyd: = 1.00 ± 0.04 ps
6
4
2
0A
S /
104
5.02.50.0
Time / ps
Thd: = 540 ± 40 fs6
4
2
0
A /
104
5.02.50.0
Time / ps
Ado: = 290 ± 40 fs
6
4
2
0
A /
104
5.02.50.0
Time / ps
Guo: = 460 ± 40 fs
DNA
RNA
Role of Conical Intersections in the Radiationless Decay of DNA Monomers:
Cytosine
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.
Conical intersections are a likely mechanism for the
ultrafast lifetimes of cytosine and the other DNA bases.
Nucleic Acid Multimers Photophysics:The Role of Base Stacking and Base
Pairing
Effect of Base Stacking Interactions
275.6 nm,0.0266H -> L 78%
H-1 -> L+1 22%
263.6 nm,0.0298H -> L+1 60%H-1 -> L 40%
S0
S1
S2
H
L L+1
H-1
TD-DFT/B3LYP/6-311G(d,p)
1.0
0.8
0.6
0.4
0.2
0.0
As /
10
3
420-2
Time / ps
6 810
2 4 6 8100
2
ApC AMP + CMP
1.5
1.0
0.5
0.0
As /
10
3
420-2
Time / ps
6 810
2 4 6 8100
TpdA AMP + TMP
1.2
1.0
0.8
0.6
0.4
0.2
0.0
As /
10
3
420-2
Time / ps
610
2 4 6100
2 4
ApA AMP
Dinucleotides: stack ↔ unstackNucleotides: unstack
AdeA-AA R = 3 Å R = 4 Å R = 5 Å R = 6 Å
HOMO
A-AA6
LUMO
TD-DFT/B3LYP/6-311G(d,p) Calculations of A-Form ApA
Electronic Coupling versus Interchromophoric Distance
5.2
5.0
4.8
4.6
Exc
itatio
n E
ne
rgy
/ eV
6.05.04.03.0Distance / Å
S1
S2
E= 0.2 eV
AA AMP
R
3000
2500
2000
1500
1000
500
Exc
ition
Spl
ittin
g /
cm-1
-80 -40 0 40 80
P-O Torsion Angle / degrees
Crespo-Hernández, C.E.; Marai, C.N.J. AIP Conference Proceedings 2007, 963, 607.
Reversible Redox Potentials of DNA NucleosidesCrespo-Hernández, C.E.; Close, M. D.; Gorb, L.; Leszczynski J. Phys. Chem. B 2007, 111, 5386.
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.
The decay rates of the long-lived states increase with increasing driving force for charge recombination as expected in the Marcus inverted region.
G° E°ox - E°red IP - EA
Role of the Driving Force for Charge Separation
-25
-20
-15
-10
-5
0
5
A /
103
604020
Time / ps100
2 3 4 5 61000
buffer D2O
d(GC)9•d(GC)9
-12
-8
-4
0
A /
103
5040302010
Time / ps100
2 3 4 5 61000
buffer D2O
d(IC)9•d(IC)9
ΔG(GC) > ΔG(AT) > ΔG(IC)
-20
-15
-10
-5
0
A /
10
-3
1050 100 1000Time / ps
250 nm
H2O D2O
d(AT)9•d(AT)9
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.
Excited State Dynamics and DNA Photochemistry:Making Connections
T<>T photodimers account
for ~90% of DNA Damage*
UV
Singlet or triplet state?
Formation time scale?
* Cadet, J.; Vigny, P. In Bioorganic Photochemistry; Morrison, H., Ed.; Wiley: New York, 1990; Vol.1, p 1.
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.
Thymine Dimerization in DNA is an Ultrafast Reaction
Steady State IR fs-Time-Resolved IR
0.50
0.25
0.00As /
10
-3
420-2 100 1000
570 nm
5'-TTTTTTTTTTTTTTTTTT-3' TMP
Time / ps
fs-Transient Absorption
= 740 12 fs
Law, Y.K.; Azadi, J.; Crespo-Hernández, C.E.; Cohen, B.; Kohler, B. Biophysical J. 2008, in press.
Prediction of T<>T Yields from MD Simulations
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.
• 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.
Conclusions
Our combined experimental and computational studies have shown:
Conceptual Pump-Probe Transient Absorption Experiment
S0
S1
kr knr
Sn
Energy
4.2 eV
0 eV
6 eV
Delay / fs
OD
Time / fs
A
Sn
S1
S0
t < 0 t = 0 t = t1 t = tn
…
……
…
“initiation”
pump
probe
probe delay
pump
probe
0-
probe600 nm
pump267 nm
PD/PMT
Lockin Amplifier
Monochrometer
Femtosecond Pump-Probe Transient Absorption Setup
OPA; 230-1300 nm
Beam Blocker
1cm
Water Cell
WLC; 350-900 nm
Mira, Evolution, Legend
2.9W, 800 nm, 35 fs
1mm Flow Cell
267 nm
mm BBO
Prism-Compressor
Computer Controlled Wave Plate
Optical Chopper
Polarizer
mm BBODelay Stage
400 nm
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.
1.0
0.8
0.6
0.4
0.2
0.0
As (
nor
mal
ize
d)
5004003002001000
Time / ps
T = 26 °C T = 34 °C T = 52 °C
6
4
2
0
As /
104
1086420-2
Time / ps
26 °C 34 °C 52 °C
Temperature Dependence of the Decays of PolyA and AMP
PolyA
AMP
Crespo-Hernández, C.E.; Kohler, B. J. Phys. Chem. B 2004, 108, 11182.
0
A (
No
rma
lize
d)
2 4 6100
2 4 61000
0
A (
No
rma
lize
d)
100
Time delay / ps
(a)
poly(A)n
(A)4
ApA
(b)
? poly(A)n
? (A)4
? ApA
Excimer State is Localized between two Stacked Bases.