1. Università degli studi Federico Secondo di Napoli, Italy
Ab initio molecular excitation study of Benzyluracil: A model for DNA-Protein cross-linking
Marco Micciarelli
Università degli studi Federico Secondo di Napoli, Italy

2. -Senior Researcher Dr. Attila Bende
ATLAS PROIECT ( ): Development of Laser-Based Technologies and Prototype Instruments for Genome-Wide Chromatin ImmunoPrecipitation Analyses. Overall budget funded by EU about 3 millions €, prinicipally based in Napoli. (PI of the progect prof Lucia Altucci, Second University of Napoli)
Molecular and Biomolecular Physics Department Cluj-Napoca (RO) group (mostly numerical so far…):
-Senior Researcher Dr. Attila Bende
-Principal Investigator Dr. Valer Tosa
-Researcher Katalin Kovacs
-Marco Micciarelli (collaborator)
Biophotonics Napoli group (mostly experimental so far…):
-Assoc.Prof. Raffaele Velotta
-Assis. Prof Carlo Altucci
-Dr. Rosario Esposito
-Marco Micciarelli (Master student)
Open Day Material 03/04/2009
Open Day Material 03/04/2009

3. DNA-Protein Cross-Linking
-Interaction between DNA and Proteins in general are fundamental in biological sciences
-Two different philosophies of study: In vitro V.S. In vivo
-Cross-Links are bonds that link
one polymer chain to another with
a covalent bond
-DNA-Protein Cross-Linking allow to
study less stable reactions in vivo
Open Day Material 03/04/2009

4. Two kinds of Cross-link
Chemical catalyzers
(formaldeide)
Two kinds of Cross-link
UV-lamps
(molecular excitation)
UV-fs-laser cross-link??
Possible advantages?
1- wider applicability
2-Higher yield (if the
process is nonlinear)
3- still alive cells after
treatment
Open Day Material 03/04/2009

5. Model systems for DNA-Protein Cross-Linking
Uracile(Thymine)/Benzene(Phenylalanine)
6-Benzyluracil Photocyclysation
5-Benzyluracile Photocyclysation
See:
DNA-Protein Cross-Linking: Model Systems for Pyrimidine-Aromatic Amino Acid Cross-Linking
Guangxing Sun, Christopher J. Fecko, Robert B. Nicewonger, Watt W. Webb, and Tadhg P. Begley: ORGANIC LETTERS, Vol.8, 681 (2006)
Open Day Material 03/04/2009

6. Gaussian03 quantum chemistry program package
Theoretical moldel for molecular excitation:
Born Oppenheimer Approximation
The Hartree Fock approximation (one Slater determinant)
Configuration Interation
Huge number of determinants….
CASSCF (14,10)
Geometry optimization
(14,10) -> 7 occupied orbitals
-> 3 unoccupied orbitals
Gaussian03 quantum chemistry program package
Open Day Material 03/04/2009

7. RESULTS:
The uracil S2 geometry is more favorable for photocyclization transition
The 5-Benzyluracile shows a stronger tendency to reach the final structure than 6-Benzyluracil
For λ = 254 nm the highest cross-linking rate is obtained for 5-Benzyluracil
Open Day Material 03/04/2009

8. NIRDIMT Data Center’s Molecular Modeling Linux Cluster:
Workstations:
- 1 x of AMD Opteron 2224, 2xdual-core, with 16 GB RAM memory
2 x of AMD Opteron 275, 2xdual-core, with 8 GB RAM memory
1 x of AMD Opteron 265, 2xdual-core, with 8 GB RAM memory
2 x of AMD Opteron 265, 2xdual-core, with 4 GB RAM memory
3 x of Intel Quad-core 5430, 2xquad-core, with 16 GB RAM memory
Operating system:
- OpenSuSE 10.3 distribution for x86_64 Linux
Molecular Modeling Software License:
- Gaussian 03 (C0.2), Molpro (2008.1), Amber 9, NWChem (5.1.1), DFTB+, WASP
Open Day Material 03/04/2009

9. Thank you for your attention
Aims…
-Joining a wide and qualified scientific community to share our research
with interdisciplinary frame is essential to face the behavior of complex systems
& Expectations
-To find within Grisù hardware and software resources capable to provide
Answers to our quests and to trigger significant progresses for our scientific
research
Thank you for your attention
Open Day Material 03/04/2009