Excess energy flow in dna bench and computer experiments working in unison
Download
1 / 21

Excess Energy Flow in DNA: Bench and Computer Experiments Working in Unison - PowerPoint PPT Presentation


  • 108 Views
  • Uploaded on

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

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Excess Energy Flow in DNA: Bench and Computer Experiments Working in Unison' - arissa


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
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: [email protected]

Ohio Supercomputer Center

Columbus, Ohio

April 4, 2008


Acknowledgement
Acknowledgement Working in Unison

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


Ohio Supercomputer Center Allocations Working in Unison

(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.


Working in Unison

Ultrafast ExcitedState Dynamics of Nucleic Acids


S Working in Unison1 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.


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.


Nucleic Acid Multimers Photophysics: DNA Monomers: Cytosine

The Role of Base Stacking and Base Pairing


TD-DFT/B3LYP/6-311G(d,p) DNA Monomers: Cytosine

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


A-AA DNA Monomers: Cytosine

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


Reversible Redox Potentials of DNA Nucleosides DNA Monomers: Cytosine

Crespo-Hernández, C.E.; Close, M. D.; Gorb, L.; Leszczynski J. Phys. Chem. B2007, 111, 5386.


Charge Transfer Character of the Excimer/Exciplex DNA Monomers: Cytosine

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.


Role of the Driving Force for Charge Separation DNA Monomers: Cytosine

  • 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)


Singlet or triplet state? DNA Monomers: Cytosine

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.


Thymine Dimerization in DNA is an Ultrafast Reaction DNA Monomers: Cytosine

  • 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


Prediction of t t yields from md simulations
Prediction of T<>T Yields from MD Simulations DNA Monomers: Cytosine

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.


Conclusions DNA Monomers: Cytosine

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.


DNA Monomers: Cytosine

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


Femtosecond Pump-Probe Transient Absorption Setup DNA Monomers: Cytosine

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


Ultrafast Deactivation Channel for Thymine Dimerization DNA Monomers: Cytosine

Boggio-Pasqua, M.; Groenhof, G.; Schäfer, L.V.; Grubmüller, H.; Robb, M.A. J. Am. Chem. Soc.2007, 129, 10996.


Temperature dependence of the decays of polya and amp
Temperature Dependence of the Decays of PolyA and AMP DNA Monomers: Cytosine

Crespo-Hernández, C.E.; Kohler, B. J. Phys. Chem. B2004, 108, 11182.

Excimer State is Localized between two Stacked Bases.

PolyA

AMP


ad