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185 results on '"Kubař, Tomáš"'

4. Reaction Path Averaging: Characterizing the Structural Response of the DNA Double Helix to Electron Transfer

Author

Kolář, Michal H. and Kubař, Tomáš

Subjects
Physics - Chemical Physics, Condensed Matter - Soft Condensed Matter, Physics - Biological Physics, Physics - Computational Physics
Abstract

A polarizable environment, prominently the solvent, responds to electronic changes in biomolecules rapidly. The knowledge of conformational relaxation of the biomolecule itself, however, may be scarce or missing. In this work, we describe in detail the structural changes in DNA undergoing electron transfer between two adjacent nucleobases. We employ an approach based on averaging of tens to hundreds of thousands of nonequilibrium trajectories generated with molecular dynamics simulation, and a reduction of dimensionality suitable for DNA. We show that the conformational response of the DNA proceeds along a single collective coordinate that represents the relative orientation of two consecutive base pairs, namely, a combination of helical parameters shift and tilt. The structure of DNA relaxes on time scales reaching nanoseconds, contributing marginally to the relaxation of energies, which is dominated by the modes of motion of the aqueous solvent. The concept of reaction path averaging (RPA), conveniently exploited in this context, makes it possible to filter out any undesirable noise from the nonequilibrium data, and is applicable to any chemical process in general., Comment: 45 pages, 20 figures, published, added Supplementary information

Published
2017
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5. Reduction pathway of glutaredoxin 1 investigated with QM/MM molecular dynamics using a neural network correction.

Author

Böser, Julian, Kubař, Tomáš, Elstner, Marcus, and Maag, Denis

Subjects
*MOLECULAR dynamics, *GLUTAREDOXIN, *GIBBS' energy diagram, *DENSITY functionals, *PHASE space
Abstract

Glutaredoxins are small enzymes that catalyze the oxidation and reduction of protein disulfide bonds by the thiol–disulfide exchange mechanism. They have either one or two cysteines in their active site, resulting in different catalytic reaction cycles that have been investigated in many experimental studies. However, the exact mechanisms are not yet fully known, and to our knowledge, no theoretical studies have been performed to elucidate the underlying mechanism. In this study, we investigated a proposed mechanism for the reduction of the disulfide bond in the protein HMA4n by a mutated monothiol Homo sapiens glutaredoxin and the co-substrate glutathione. The catalytic cycle involves three successive thiol–disulfide exchanges that occur between the molecules. To estimate the regioselectivity of the different attacks, classical molecular dynamics simulations were performed and the trajectories analyzed regarding the sulfur–sulfur distances and the attack angles between the sulfurs. The free energy profile of each reaction was obtained with hybrid quantum mechanical/molecular mechanical metadynamics simulations. Since this required extensive phase space sampling, the semi-empirical density functional tight-binding method was used to describe the reactive cysteines. For an accurate description, we used specific reaction parameters fitted to B3LYP energies of the thiol–disulfide exchange and a machine learned energy correction that was trained on coupled-cluster single double perturbative triple [CCSD(T)] energies of thiol–disulfide exchanges. Our calculations show the same regiospecificity as observed in the experiment, and the obtained barrier heights are about 12 and 20 kcal/mol for the different reaction steps, which confirms the proposed pathway. [ABSTRACT FROM AUTHOR]

Published
2022
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6. Structural stability versus conformational sampling in biomolecular systems: Why is the charge transfer efficiency in G4-DNA better than in double-stranded DNA?

Author

Woiczikowski, P. Benjamin, Kubař, Tomáš, Gutiérrez, Rafael, Cuniberti, Gianaurelio, and Elstner, Marcus

Subjects
Condensed Matter - Materials Science
Abstract

The electrical conduction properties of G4-DNA are investigated using a hybrid approach, which combines electronic structure calculations, molecular dynamics (MD) simulations, and the formulation of an effective tight-binding model Hamiltonian. Charge transport is studied by computing transmission functions along the MD trajectories. Though G4-DNA is structurally more stable than double-stranded DNA (dsDNA), our results strongly suggest that the potential improvement of the electrical transport properties in the former is not necessarily related to an increased stability, but rather to the fact that G4 is able to explore in its conformational space a larger number of charge-transfer active conformations. This in turn is a result of the non-negligible interstrand matrix elements, which allow for additional charge transport pathways. The higher structural stability of G4 can however play an important role once the molecules are contacted by electrodes. In this case, G4 may experience weaker structural distortions than dsDNA and thus preserve to a higher degree its conduction properties., Comment: 12 pages, 11 figures, 2 tables + supporting information

Published
2010
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7. Tracking the Electron Transfer Cascade in European Robin Cryptochrome 4 Mutants

Author

Timmer, Daniel, primary, Frederiksen, Anders, additional, Lünemann, Daniel C., additional, Thomas, Anitta R., additional, Xu, Jingjing, additional, Bartölke, Rabea, additional, Schmidt, Jessica, additional, Kubař, Tomáš, additional, De Sio, Antonietta, additional, Solov’yov, Ilia A., additional, Mouritsen, Henrik, additional, and Lienau, Christoph, additional

Published
2023
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14. Coupled-perturbed DFTB-QM/MM metadynamics: Application to proton-coupled electron transfer.

Author

Gillet, Natacha, Elstner, Marcus, and Kubař, Tomáš

Subjects
DENSITY functional theory, QUANTUM mechanics, CHARGE exchange, MOLECULAR dynamics, COMPUTATIONAL chemistry, PROTON transfer reactions
Abstract

We present a new concept of free energy calculations of chemical reactions by means of extended sampling molecular dynamics simulations. Biasing potentials are applied on partial atomic charges, which may be combined with atomic coordinates either in a single collective variable or in multi-dimensional biasing simulations. The necessary additional gradients are obtained by solving coupled-perturbed equations within the approximative density-functional tight-binding method. The new computational scheme was implemented in a combination of Gromacs and Plumed. As a prospective application, proton-coupled electron transfer in a model molecular system is studied. Two collective variables are introduced naturally, one for the proton transfer and the other for the electron transfer. The results are in qualitative agreement with the extended free simulations performed for reference. Free energy minima as well as the mechanism of the process are identified correctly, while the topology of the transition region and the height of the energy barrier are only reproduced qualitatively. The application also illustrates possible difficulties with the new methodology. These may be inefficient sampling of spatial coordinates when atomic charges are biased exclusively and a decreased stability of the simulations. Still, the new approach represents a viable alternative for free energy calculations of a certain class of chemical reactions, for instance a proton-coupled electron transfer in proteins. [ABSTRACT FROM AUTHOR]

Published
2018
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23. Orthogonal 19 F-Labeling for Solid-State NMR Spectroscopy Reveals the Conformation and Orientation of Short Peptaibols in Membranes

Author

Grage, Stephan L., primary, Kara, Sezgin, additional, Bordessa, Andrea, additional, Doan, Véronique, additional, Rizzolo, Fabio, additional, Putzu, Marina, additional, Kubař, Tomáš, additional, Papini, Anna Maria, additional, Chaume, Grégory, additional, Brigaud, Thierry, additional, Afonin, Sergii, additional, and Ulrich, Anne S., additional

Published
2018
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25. “siRNA traffic lights”: arabino-configured 2′-anchors for fluorescent dyes are key for dual color readout in cell imaging

Author

Steinmeyer, Jeannine, primary, Walter, Heidi-Kristin, additional, Bichelberger, Mathilde A., additional, Schneider, Violetta, additional, Kubař, Tomáš, additional, Rönicke, Franziska, additional, Olshausen, Bettina, additional, Nienhaus, Karin, additional, Nienhaus, Gerd Ulrich, additional, Schepers, Ute, additional, Elstner, Marcus, additional, and Wagenknecht, Hans-Achim, additional

Published
2018
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32. Fragment orbital based description of charge transfer in peptides including backbone orbitals

Author

Heck, Alexander, Woiczikowski, P. Benjamin, Kubař, Tomáš, Welke, Kai, Niehaus, Thomas, Giese, Bernd, Skourtis, Spiros, Elstner, Marcus, and Steinbrecher, Thomas B.

Abstract

Charge transfer in peptides and proteins can occur on different pathways, depending on the energetic landscape as well as the coupling between the involved orbitals. Since details of the mechanism and pathways are difficult to access experimentally, different modeling strategies have been successfully applied to study these processes in the past. These can be based on a simple empirical pathway model, efficient tight binding type atomic orbital Hamiltonians or ab initio and density functional calculations. An interesting strategy, which allows an efficient calculations of charge transfer parameters, is based on a fragmentation of the system into functional units. While this works well for systems like DNA, where the charge transfer pathway is naturally divided into distinct molecular fragments, this is less obvious for charge transfer along peptide and protein backbones. In this work, we develop and access a strategy for an effective fragmentation approach, which allows one to compute electronic couplings for large systems along nanosecond time scale molecular dynamics trajectories. The new methodology is applied to a solvated peptide, for which charge transfer properties have been studied recently using an empirical pathway model. As could be expected, dynamical effects turn out to be important, which emphasizes the importance of using effective quantum approaches which allow for sufficient sampling. However, the computed rates are orders of magnitude smaller than experimentally determined, which indicates the shortcomings of present modeling approaches.

Published
2014

35. Orthogonal 19F‐Labeling for Solid‐State NMR Spectroscopy Reveals the Conformation and Orientation of Short Peptaibols in Membranes.

Author

Grage, Stephan L., Kara, Sezgin, Bordessa, Andrea, Doan, Véronique, Rizzolo, Fabio, Putzu, Marina, Kubař, Tomáš, Papini, Anna Maria, Chaume, Grégory, Brigaud, Thierry, Afonin, Sergii, and Ulrich, Anne S.

Subjects
ORGANIC solid state chemistry, NUCLEAR magnetic resonance spectroscopy, AMINO acids, AMINO compounds, ARTIFICIAL membranes
Abstract

Abstract: Peptaibols are promising drug candidates in view of their interference with cellular membranes. Knowledge of their lipid interactions and membrane‐bound structure is needed to understand their activity and should be, in principle, accessible by solid‐state NMR spectroscopy. However, their unusual amino acid composition and noncanonical conformations make it very challenging to find suitable labels for NMR spectroscopy. Particularly in the case of short sequences, new strategies are required to maximize the structural information that can be obtained from each label. Herein, l‐3‐(trifluoromethyl)bicyclopent[1.1.1]‐1‐ylglycine, (R)‐ and (S)‐trifluoromethylalanine, and 15N‐backbone labels, each probing a different direction in the molecule, have been combined to elucidate the conformation and membrane alignment of harzianin HK‐VI. For the short sequence of 11 amino acids, 12 orientational constraints have been obtained by using 19F and 15N NMR spectroscopy. This strategy revealed a β‐bend ribbon structure, which becomes realigned in the membrane from a surface‐parallel state towards a membrane‐spanning state, with increasing positive spontaneous curvature of the lipids. [ABSTRACT FROM AUTHOR]

Published
2018
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43. Charge transfer in model peptides: obtaining Marcus parameters from molecular simulation

Author

Heck, Alexander, Woiczikowski, P. Benjamin, Kubař, Tomáš, Giese, Bernd, Elstner, Marcus, Steinbrecher, Thomas B., Heck, Alexander, Woiczikowski, P. Benjamin, Kubař, Tomáš, Giese, Bernd, Elstner, Marcus, and Steinbrecher, Thomas B.

Abstract

Charge transfer within and between biomolecules remains a highly active field of biophysics. Due to the complexities of real systems, model compounds are a useful alternative to study the mechanistic fundamentals of charge transfer. In recent years, such model experiments have been underpinned by molecular simulation methods as well. In this work, we study electron hole transfer in helical model peptides by means of molecular dynamics simulations. A theoretical framework to extract Marcus parameters of charge transfer from simulations is presented. We find that the peptides form stable helical structures with sequence dependent small deviations from ideal PPII helices. We identify direct exposure of charged side chains to solvent as a cause of high reorganization energies, significantly larger than typical for electron transfer in proteins. This, together with small direct couplings, makes long-range superexchange electron transport in this system very slow. In good agreement with experiment, direct transfer between the terminal amino acid side chains can be dicounted in favor of a two-step hopping process if appropriate bridging groups exist.

Published
2012

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