My current projects in general

RNA aptamers: classical MD studies CYP: docking, semiempirical QC Arthritis proteins: classical MD studies
E Starikov. Talk at GFNL, Sevilla, April 1, 2005

Molecular Modelling of Nucleic Acids: How Quantum Chemistry Might Help

Frontier orbitals in DNA Nature of excited states in DNA Nature of disorder in DNA
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Molecular Modelling of Nucleic Acids: How Quantum Chemistry Might Help

Electron-phonon coupling in DNANA Electron correlations in DNA DNA doping

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Molecular Modelling of Nucleic Acids: How Quantum Chemistry Might Help

General aim:
Relationship between DNA electronic structure and its properties
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Molecular Modelling of Nucleic Acids: How Quantum Chemistry Might Help

Extended Hckel: YAeHMOP Semiempirical: MOPAC (PM3-CI) Hartree-Fock ab initio: GAUSSIAN-98, GAMESS-US DFT: FIREBALL
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Methods

FIREBALL
Authors: Prof. O.F. Sankey, Prof. J.P. Lewis et. al.

2 Main Features:
-Kohn-Sham functional -> Harris-Foulkes functional (faster achievement of self-consistency) -One-electron Schrdinger equation in terms of slightly excited atomic orbitals (fireballs) -> N-scaling instead of conventional N3-scaling

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Poly(dA)-poly(dT) fiber, +Na & H2O

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Poly(dA)-poly(dT) density of states

DNA + water + Na cations, true 3D crystal, extended Hckel

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dA-dT Watson-Crick base pair, HOMO

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dA-dT Watson-Crick base pair, LUMO

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dG-dC Watson-Crick base pair, HOMO

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dG-dC Watson-Crick base pair, LUMO

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dAdT/dAdT bp step: Frontier orbitals

LUMO HOMO
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dGdC/dGdC base pair step, HOMO

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dGdC/dGdC base pair step, LUMO

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DNA DISORDER
Marriage

between FIREBALL and classical MD

System under study: poly(dA)10-poly(dT)10

With water of hydration, but without counterions

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Ordered, B-DNA:

Disordered, after 2 ns MD:

->
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Quantifying DNA Disorder

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Time evolution of HOMO (Ade residue)

Time Step 1.5 ps
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Dynamical disorder in DNA: Sources ?

Dynamical attenuation of base coupling

Thermal fluctuations of counterionwater environment

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Electron-phonon coupling in DNA

Tight binding for electrons, linear harmonic approximation for vibrations
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Electron-phonon coupling in DNA

R0

- changes in l0 a rn - changes in R0 due to H-bond stretching q0

dn n-1

l0

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Electron-phonon coupling in DNA

dGdC/ dGdC
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dAdT/ dAdT
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Electron-phonon coupling in DNA

- The helical twist and pitch dynamics is not so strongly coupled to electron degrees of freedom, as compared to the Watson-Crick H-bonds stretching. - The coupling coefficients for the latter one to on-site electron energies in poly(dA)-poly(dT) and poly(dG)-poly(dC) are of the same absolute value, but with opposite signs. - The coupling coefficient for the latter one to electron-hopping matrix elements in poly(dA)-poly(dT) is one order of magnitude less than that in poly(dG)-poly(dC).

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Electron-phonon coupling in DNA

These equations describe polaron motion in DNA

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- Poly(dA)-poly(dT) POLARON is less localized than that in poly(dG)-poly(dC). - Polaron deformations in poly(dA)-poly(dT): H-bond contractions, in poly(dG)-poly(dC) they are H-bond stretchings. - Generally, poly(dA)-poly(dT) is possessed of worsepolaron conductivepropertiesthan poly(dG)-poly(dC).
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Electron-phonon coupling in DNA

Electron-electron correlations in DNA

General Hubbard Hamiltonian Only one frontier orbital per molecular unit is assumed
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Electron-electron correlations in DNA

Both A- and B-DNA conformations

dGdC/ dGdC

Both excess electrons and holes

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dAdT/ dAdT
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Electron-electron correlations in DNA

FortunelliPainelli method, PM3-CI Hamiltonian.
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Electron-electron correlations in DNA

H o l e s : U is lower for GC/GC than for AT/AT, V is almost the same. There is significant conformation dependence for t in GC/GC. Excess electrons: U is negative ! The t values in GC/GC are extremely low. V is almost the same as for the holes.
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DNA docking with molecular oxygen

AT/AT, B-form, O2 in the major and water in the minor groove
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DNA docking with molecular oxygen

GC/GC, B-form, O2 both in the minor and in the major groove
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DNA docking: ATAT, no molecular oxygen

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DNA docking: ATAT, no molecular oxygen

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DNA docking: ATAT, molecular oxygen

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DNA docking: ATAT, molecular oxygen

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DNA docking: ATAT, oxygen and water

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DNA docking: ATAT, oxygen and water

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DNA docking: GCGC, no molecular oxygen

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DNA docking: GCGC, no molecular oxygen

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DNA docking: GCGC, O2 in minor groove

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DNA docking: GCGC, O2 in minor groove

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DNA docking: GCGC, O2 in major groove

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DNA docking: GCGC, O2 in major groove

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DNA docking: GCGC, O2, the both grooves

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DNA docking: GCGC, O2, the both grooves

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Future prospects
Base pair sequence effects Longer DNA fragments Ab initio QC vs. semiempirical QC
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Acknowledgements to collaborators
Prof. Lennart Nilsson, KI, Sweden Prof. N. Vermeulen, VU Amsterdam, Holland Prof. J. Lewis, Brigham-Young Univ., USA Dr. D. Hennig, FU Berlin, Germany
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Special acknowledgement

Dr. Shigenori Tanaka, R&D Toshiba

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