|
|
Structural Interpretation of NMR Spectroscopic Parameters in Nucleic Acids
Fukal, Jiří ; Sychrovský, Vladimír (advisor) ; Hrabal, Richard (referee) ; Munzarová, Markéta (referee)
Title: Structural Interpretation of NMR Spectroscopic Parameters in Nucleic Acids Author: Mgr. Jiří Fukal Supervisor: Dr. Vladimír Sychrovský Institutions: Charles University, Faculty of Mathematics and Physics, and Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry Abstract: Nuclear Magnetic Resonance (NMR) is versatile spectroscopy technique applicable to determination of both chemical and 3D structure of molecules. Elementary characterization of peptides, proteins and nucleic acids employs the 1 H and 13 C NMR measurements. Probing of 15 N and 17 O atoms usually requires advanced chemical preparation of molecules (labelling with relevant isotopes). 31 P NMR is in that regard exceptional due to 100% natural abundance of the isotope. Hence, NMR structural studies of a nucleic acid's backbone are aimed at the phosphate group. Pertinent spectral parameters include δ31P NMR shift and J-couplings involving the phosphorus atom (e.g. 3 JP,H3'). Structural interpretation of NMR spectra requires usage of adequate quantum chemistry method (QM method) and inclusion of effects due to molecular dynamic (MD). That is why plausible interpretation of the spectral parameters in nucleic acids may become computationally demanding. The benchmark of QM methodology for 31 P NMR calculation made possible...
|
|
|
Determination of structure and dynamics of biomolecules by theoretical calculations of NMR spectroscopic parameters
Benda, Ladislav ; Sychrovský, Vladimír (advisor) ; Munzarová, Markéta (referee) ; Hrabal, Richard (referee)
iv Abstract Subject: Determination of structure and dynamics of biomolecules by theoretical calcu- lations of NMR spectroscopic parameters Author: Ladislav Benda, ladislav.benda@gmail.com Department/Institute: Institute of Organic Chemistry and Biochemistry, AS CR Supervisor: Dr. Vladim'ır Sychrovsk'y, Institute of Organic Chemistry and Biochemistry, AS CR, vladimir.sychrovsky@uochb.cas.cz Abstract: This doctoral work was focused on theoretical modeling of nuclear magnetic resonance (NMR) parameters in peptides and nucleic acids. Dependences of NMR para- meters on molecular structure and solvation were primarily modeled. Great emphasis was put on the comparison of the calculated data with the NMR experiment. The molecular models studied included the l-alanyl-l-alanine di-peptide (AA) and the phosphate group of nucleic acid backbone. Conformations of all three charged forms of AA in solution were determined and the respective pH-induced changes of experimental NMR chemical shifts and nuclear spin-spin coupling constants were explained. Dependences of NMR cross-correlated relaxation rates on the AA backbone geometry were calibrated. The 31 P NMR parameters in nucleic acid phosphate were systematically calculated in dependence on the backbone conformation and the phosphate solvation pattern. Qualitative rules...
|
|
| |
|
| |
|
| |
|
|
Combined QM/MM decsription of interaction of Ru(II) 'piano-stool' organometallic complexes with oligomer models of DNA
Zábojníková, Tereza ; Burda, Jaroslav (advisor) ; Sychrovský, Vladimír (referee)
This work is focused on 4 organometalic drugs with "piano-stool" Ru(II) structure: these complexes are: nalidixic acid, thio-nalidixic acid, ofloxacin and cinoxacin. Thermodynamic parameters of three type of reactions with water were analyzed for each of these four complexes. All complexes were examined in both protonated and deprotonated state, since all of these complexes are acids and they behave differently in acidic and neutral enviroment. Optimalization was performed using DFT method B3PW91 in basis 6-31+G*. Energies were calculated in basis 6-311++G(2df,2pd) using DFT method B3LYP and NPA analysis was performed for finding partial charges on atoms.
|
|
| |
|
|
NMR Study of Oligonucleotide Structures
Římal, Václav ; Štěpánková, Helena (advisor) ; Spěváček, Jiří (referee) ; Sychrovský, Vladimír (referee)
Title: NMR Study of Oligonucleotide Structures Author: Václav Římal Department: Department of Low-Temperature Physics Supervisor: Prof. RNDr. Helena Štěpánková, CSc., Department of Low- Temperature Physics Abstract: The dynamics of nucleic acids plays a fundamental role in the interactions with proteins. Some processes are governed by changes in DNA stability and flexibility caused by sequence alterations or chemical modifications without substantial structural impact. We employed line-shape analysis of variable-temperature 1H NMR spectra to deeply investigate the melting transition of DNA structures. We observed a significant influence of the sequence beyond the nearest neighbours on chemical shifts and thermodynamics of the double helix. The CpG motif is especially sensitive to its distant surroundings and for a particular oligonucleotide it was even found to undergo an unexpected local conformational transition. A strong cooperativity in the duplex dis- ruption was witnessed by both the equilibrium and kinetic aspects as well as by distant effects of cytosine methylation. We propose a two-state melt- ing scheme also for a fragment of a transcription element proved here to fold as a hairpin with a six-membered loop. In addition, we describe the properties of self-assemblies of riboguanosine and...
|
|
|
Determination of structure and dynamics of biomolecules by theoretical calculations of NMR spectroscopic parameters
Benda, Ladislav ; Sychrovský, Vladimír (advisor) ; Munzarová, Markéta (referee) ; Hrabal, Richard (referee)
iv Abstract Subject: Determination of structure and dynamics of biomolecules by theoretical calcu- lations of NMR spectroscopic parameters Author: Ladislav Benda, ladislav.benda@gmail.com Department/Institute: Institute of Organic Chemistry and Biochemistry, AS CR Supervisor: Dr. Vladim'ır Sychrovsk'y, Institute of Organic Chemistry and Biochemistry, AS CR, vladimir.sychrovsky@uochb.cas.cz Abstract: This doctoral work was focused on theoretical modeling of nuclear magnetic resonance (NMR) parameters in peptides and nucleic acids. Dependences of NMR para- meters on molecular structure and solvation were primarily modeled. Great emphasis was put on the comparison of the calculated data with the NMR experiment. The molecular models studied included the l-alanyl-l-alanine di-peptide (AA) and the phosphate group of nucleic acid backbone. Conformations of all three charged forms of AA in solution were determined and the respective pH-induced changes of experimental NMR chemical shifts and nuclear spin-spin coupling constants were explained. Dependences of NMR cross-correlated relaxation rates on the AA backbone geometry were calibrated. The 31 P NMR parameters in nucleic acid phosphate were systematically calculated in dependence on the backbone conformation and the phosphate solvation pattern. Qualitative rules...
|
|
|
Combined QM/MM decsription of interaction of Ru(II) 'piano-stool' organometallic complexes with oligomer models of DNA
Zábojníková, Tereza ; Burda, Jaroslav (advisor) ; Sychrovský, Vladimír (referee)
This work is focused on 4 organometalic drugs with "piano-stool" Ru(II) structure: these complexes are: nalidixic acid, thio-nalidixic acid, ofloxacin and cinoxacin. Thermodynamic parameters of three type of reactions with water were analyzed for each of these four complexes. All complexes were examined in both protonated and deprotonated state, since all of these complexes are acids and they behave differently in acidic and neutral enviroment. Optimalization was performed using DFT method B3PW91 in basis 6-31+G*. Energies were calculated in basis 6-311++G(2df,2pd) using DFT method B3LYP and NPA analysis was performed for finding partial charges on atoms.
|
guest ::
