E Starikov- Molecular Modelling of Nucleic Acids: How Quantum Chemistry Might Help

8/3/2019 E Starikov- Molecular Modelling of Nucleic Acids: How Quantum Chemistry Might Help

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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


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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

E Starikov, Sevilla 2005 2


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Electron-phonon coupling in DNA Electron correlations in DNA

DNA doping



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General aim:

Relationship betweenDNA electronic structureand its propertiesE Starikov, Sevilla 2005 4


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MethodsExtended Hckel: YAeHMOP

Semiempirical: MOPAC (PM3-CI)

Hartree-Fock ab initio: GAUSSIAN-98,GAMESS-US

DFT: FIREBALL



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FIREBALLAuthors: 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 statesDNA+

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

HOMO

LUMO



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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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QuantifyingDNA

Disorder



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Time evolution of HOMO (Ade residue)T i m eStep1.5 ps



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Dynamical disorder in DNA: Sources ?Dynamical

attenuationof base

coupling

Thermal

fluctuationsofcounterion-

waterenvironment



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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 DNAR0

a l0

q0

dn n-1 - changes in l0rn - changes inR0 due to H-bond stretching



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dGdC/

dGdC

dAdT/

dAdT



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Electron-phonon coupling in DNA- The helical twist and pitch dynamics is not so strongly coupledto electron degrees of freedom, as compared to the Watson-CrickH-bonds stretching.- The coupling coefficients for th e latter one to on-site electron energ ies in poly(dA)-poly(dT) and poly(dG)-poly(dC) are of th esame absolute value, but with opposite signs.- The coupling coefficient for th e latter one to electron-hoppingmatrix elements in poly(dA)-poly(dT) is one order of magnitude less than that in poly(dG)-poly(dC).



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These equations describepolaron motionin DNA



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Electron-phonon coupling in DNA- Poly(dA)-poly(dT) POLARON isless localizedthan that inpoly(dG)-poly(dC).- Polaron deformations inpoly(dA)-poly(dT): H-bondcontractions, in poly(dG)-poly(dC)they are H-bondstretchings.-Generally, poly(dA)-poly(dT) ispossessed of worsepolaronconductive properties thanpoly(dG)-poly(dC).



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Electron-electron correlations in DNAGeneral Hubbard

Hamiltonian

Only one frontier

orbital per molecularunit is assumed



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dGdC/

dGdC

dAdT/

dAdT

Electron-electron correlations in DNABoth A- and B-DNA conformations

Both excess electrons and holes



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Electron-electron correlations in DNAFortunelli-

Painellimethod,

PM3-CIHamiltonian.



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Electron-electron correlations in DNAH o l e s :Uis lower for GC/GC than for AT/AT, V is almostthe same. There is significant conformation dependence for tinGC/GC.E x c e s s e l e c t r o ns :U is negative ! The tvalues inGC/GC are extremely low. Vis almost the same as for the holes.



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DNA docking with molecular oxygenAT/AT, B-form,

O2 in the majorand water inthe minorgroove



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DNA docking with molecular oxygenGC/GC, B-form,

O2 both in theminor and in

the majorgroove



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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 collaboratorsProf. 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

E Starikov Sevilla 2005 49

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E Starikov- Molecular Modelling of Nucleic Acids: How Quantum Chemistry Might Help