Courses schedule

1
Courses schedule InfoChemie Mo. (Lundi) 11 to
13 (original 10-12) Credits 4 No.
students 62 -Chemistry and life science
. 112(not there) -others (informatics ) 2
(info)1 physics(?) BioInfo Mo. (Lundi) 8 to
11 (original 8-10, 12-13) Credits 3 No.
students 6 -Chemistry and life science
. 112(not there) -others (informatics ) 1
physics(?) the same guy above
2
Organization of the courses

• CHEMISTRY students
• InfoChimie (22 Lecture Projects)
• BioInfo (21 Lecture Exercises)
• Total credits 7 (43)
• OTHER students
• Lecture InfoChimie OR BioInfo
• -Projects if InfoChemie any Project
• if BioInfo Bio-oriented Projects only
  (P.B1-B4)
• -Exercises none
• Total credits 4

3
Projects InfoChimie
B. Bio-oriented Projects B1-4 E.
Electronic Structure Projects E1-3 P.
Physical Chemistry Projects P1-3 I.
Inorganic Chemistry Projects I1-2
4
B. Bio-oriented Projects
5
Ru-anticancer compounds binding to ssDNA
P. B1
Supervision C. Gossens, I. Tavernelli

• Background
• (?6-arene)Ru(pta)2 compounds kill selectively
  cancer-cells (Prof Dyson).
• ESI-MS shows loss of arene ligand upon binding to
  ssDNA.
• Atomistic binding mode unknown!
• Project
• Learn molecular modeling Materials Studio,
  AMBER, Gaussian.
• Build Ru(pta)2-ssDNA-adducts in a virtual
  environment.
• Modify/adapt existing force fields (charges, bond
  lengths, .).
• Equilibrate constraint DNA-adducts with implicit
  solvent.
• Identify possible binding modes (A, G, T, C).
• (Option Update FF and run expicit solvent
  MD.)

6
Biased random walk of HCO3 through the
enzymeHuman Carbonic Anhydrase II
P. B2
Supervision S.Giani, I. Tavernelli, R. Lins

• Background
• HCA is a Zn based enzyme that converts CO2 into
  bicarbonate.
• After the reaction occurs, the bicarbonate
  molecule has to leave the
• active site of the enzyme while a water molecule
  takes its position binding to the metal.

• Project
• Run a biased random walk of the bicarbonate
  to find the pathway connecting the active side
  with the surrounding.
• Compute the free energy profile for the same
  process.
• Method
• Classical molecular dynamics and enhanced
  sampling techniques (thermodynamic integration).

7
Exploring RNA folding mechanisms with simulated
annealing Supervision Pascal Baillod
P. B3-part1
Background

• RNA GNRA tetraloops
• Extremely common in biologically active RNAs.
• Promote proper folding of secondary and tertiary
  structures in lager RNAs.

References Fiona M. Jucker et al., J. Mol. Biol.
(1996) 264, 968-980 Höbartner et al., J. Mol.
Biol. (2003), 325, 421-431
8
Exploring RNA folding mechanisms with simulated
annealing
P. B3-part2

• Project
• Classical md simulations of hairpin RNAs.
• High temperature (simulated annealing) will allow
  to break watson-crick base pair networks, cooling
  will enable to reform different folded
  conformation h-bond networks.
• The simulation trajectories will help
  understanding existing experimental folding
  kinetics results.

9
Binding Affinities of IAP Tetrapeptide Inhibitors
P. B4
SupervisionRoberto Lins
IAPs inhibit caspase activity and are widely
expressed in cancer cells. They are likely to
play a role in both disease progression and
resistance to therapy. A number of
tetrapeptides inhibitors (SMAC analogs) and their
dissociation constants are known.
State-of-the-art Poisson-Boltzmann electrostatics
methods will be used to calculate the binding
affinitiy energies for the IAP and its
tetrapeptide inhibitors as well as our newly
proposed non-peptidic inhibitor
10
E. Electronic Structure Projects
11

Characterization of redox states of Flavin
Mononucleotide in Flavodoxins
P. E1-part 1
Supervision Michele Cascella

• Flavodoxin small electron transferases active in
  low-electron potential pathways
• Cofactor Flavin Mono Nucleotide
• Three oxidation states oxidized
  quinone/semiquinone/hydroquinone
• Redox potential highly influenced by the protein
  environment and experimentally known

Ref Bradley L. H. et al., Biochemistry, 40,
8686-8695 (2001)
12
Characterization of redox states of Flavin
Mononucleotide in Flavodoxins
P. E1-part 2
Supervision Michele Cascella
Project Parametrization of FMN in its oxidation
states, Study of dynamical properties of
Flavodoxin/FMN complex in water by means of
Classical Molecular Dynamics. (programs used
Amber and GROMACS packages).
13
Excited state deactivation mechanism in DNA base
pairs
P. E2
Supervision Ivano Tavernelli
Motivation The excited state deactivation
mechanism specific for hydrogen-bonded dimers may
account for the photostability of the
Watson-Crick base pairs in DNA. Experimental
results Femtosecond time-resolved mass
spectroscopy reveals an excited-state lifetime of
of 65 ps for the near planar hydrogen-bonded
dimer, which is significant shorter than the
lifetime of the monomers. Mechanism Conical
intersections (CI) connect the locally excited
pp state (LE) and the electronic ground state
(GS) with a pp charge-transfer state (CT) that
is strongly stabilized by the transfer of a
proton. Project Study this de-excitation
mechanism using TDDFT (time-dependent density
functional theory) calculation. -code CPMD and
TURBOMOLE. Lit T. Schultz et. al., SCIENCE,
306, 1765-8, 2004.
14
Characterisation of a Conical Intersection using
ab-initio Molecular Dynamics
P. E3
Supervision Ivano Tavernelli and Mauricio
Coutinho-Neto

• Motivation
• Conical intersections (CI) are a fundamental
  mechanism of radiation-less transition between
  adjacent potential energy surfaces (PES).
• System
• Test system Formaldimine.
• CI between first singlet excited state and the
  ground
• state
• Intramolecular charge transfer through CI in the
  
• excited state of 4-(Dimethyl)aminobenzonitrile
  (DMABN).
• Project
• - Sample a set of ground state configurations
  according to the equilibrium Boltzmann
  distribution.
• - After excitation follow the relaxation of the
  Franck-Condon population along the excited PES
  until the conical intersection is encountered.
• - Construct a pair of reaction coordinates able
  to resolve the conical intersection and
  describe the topology of the PESs at the CI.
• Tools TDDFT combined with ab initio MD (CPMD).

15
P. Physical Chemistry Projects
16
CO microsolvation in superfluid He droplets
P. P1-part 1
Supervision Michele Cascella, Ivano Tavernelli

• Nanoscale devices of general interest in modern
  physics
• Challenging objects for theoretical computations,
  as standard quantum chemical techniques either
  fail or are too expensive

Ref Cazzato et al. J Chem. Phys. 120, 9071-9076
(2004).
17
CO microsolvation in superfluid He droplets
P. P1-part 2
Supervision Michele Cascella, Ivano Tavernelli

• Project
• Determination of the equilibrium geometries
  of the CO-Hen clusters (n 1, 2,6) by
  atom-centered vdW corrected pseudopotentials.
• (Software CPMD.)
• Ref. VonLilienfeld O.A. et al., PRL, 93,
  153004-1 (2004)

18
Electronic structure of the organic conducting
polymers
P. P2-part 1
Supervision Oleg Yazyev

• The project involves the study of the band
  structures of a number of p-conjugated organic
  polymers (polyanylines, polypyrolles,
  polyphenylvinylenes, etc.) using Gaussian
  periodic boundary conditions code and the ability
  of density functional theory to predict band gaps
  (of Fermi densities of states). It requires some
  (but not too much) knowledge on the basics of
  condensed matter physics. The 2000 Nobel prize
  was awarded for the important discoveries in this
  field.

19
Electronic structure of the organic conducting
polymers
P. P2-part 2
20
EPR Parameters of Cu2 Complexes
P. P3
Supervision MariaCarola Colombo

• EPR (Electron Paramagnetic Resonance
  Spectroscopy) is a powerful tool used to collect
  information about the environment of nuclei
  possessing electrons with unpaired spin
• Project use Cu(NH3)4(H2O)22 as a model
  system to check the validity of commercial
  quantum chemistry programs (ADF, Gaussian) to
  compute EPR parameters
• Methods CPMD, ADF, Gaussian, if time allows
  QM/MM, classical MD

21

• Inorganic Chemistry
• Projects

22
Ab initio calculation of 99Tc NMR chemical
shifts in technetium coordination complexes
related to radiopharmeceuticals
P. I1-part 1
Supervision Oleg Yazyev

• The compounds of 99m technetium isotope are used
  in medical imaging. The goal of the project is
  the systematic study of the performance of
  density functional theory methods and GTO basis
  sets for accurate prediction of 99Tc NMR chemical
  shifts for a number of technetium coordination
  compounds in different oxidation states and
  coordination envi-ronment. The study of an
  importance of relativistic effects on 99Tc NMR
  chemical shifts is also an inte-resting option.

23
Ab initio calculation of 99Tc NMR chemical
shifts in technetium coordination complexes
related to radiopharmeceuticals
P. I1-part 2
99Mo
b-, 67 hr
99mTc
g, 6 hr
99Tc
b-, 2.2 X 105 yr
99Ru (Stable)
24
Description of a fluxional process in an
hexametallic cluster compound
P. I2
Supervision C. Gossens

• Background
• Intramolecular exchange studied experimentally
  and theoretically for Ir2Rh2(CO)12 (collaboration
  Prof Roulet)
• Publication chosen as hot topic paper in Dalton
  Trans. 2005
• Ir6(CO)14 I - NMR shows similar exchange
  reaction
• concerted motion 3 6 and 3 6 exchange of
  edge-bridging CO
• this results in exchange of 5 and 2 positions of
  CO
• Project
• Learn TS-search with QM-packages ADF, Gaussian
• Describe the full fluxional process (CO-ligand
  movement)
• Identify the ground-state (C2-symmetry)
• Identify the TS

top view of octahedral cluster
25
P. I3
Calculation of the chemical potentialof metal
ions in solutionA comparative study
Supervision E. Tapavizca, I. Tavernelli

• Motivation
• Calculation of chemical properties of molecules
  in solution is a challenging subject of modern
  quantum chemistry. Examples are pKa, reactivity
  indices, reaction free energies, electrochemical
  potentials and others.
• System
• Metal ions in solution (Cu, Ag, Ruthinate, )
• Project
• Compare the electrochemical half-reaction
  potential of ions in aqueous solution for the
  different setup
• Full ab-initio aqueous sample
• QM/MM setup made of a quantum ion solvated in a
  
• explicit classical bath with counter ions.
• Validation of Marcus theory for electron transfer
  (ET) processes in solution.
• Tools
• DFT based grand canonical approach numerical
  titration.