This study analyzes changes in conformation of five double-stranded DNA fragments related to binding of the single-strand selective probe osmium tetraoxide bispyridine (Os, py) to a thymine. Molecular mechanics was used to investigate four B-DNA and one A-DNA fragments including two structures containing a G.T mispair. The reactivity of a particular thymine was estimated by the difference in energies between interactions in a refined DNA fragment and the corresponding interactions in the transformed fragment with Os, py. Both calculations with and without counterions were performed and the results were in qualitative agreement with experiments. The energetically relaxed fragments with Os, py showed relatively minor global structural changes in comparison to the relaxed fragments without Os, py probe. The computed structures of fragments with Watson-Crick pairing that enable binding of Os, py had similar structural characteristics to geometries found in X-ray studies of single-base mismatches. The possible role of ions in binding Os, py to mispairs is also discussed.

• MeSH
• DNA chemie   MeSH
• guanin MeSH
• konformace nukleové kyseliny * MeSH
• krystalografie rentgenová MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• oligodeoxyribonukleotidy chemie   MeSH
• organokovové sloučeniny chemie   MeSH
• pyridiny chemie   MeSH
• sekvence nukleotidů MeSH
• software MeSH
• thymin MeSH
• vodíková vazba MeSH
• zastoupení bazí MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• DNA MeSH
• guanin MeSH
• oligodeoxyribonukleotidy MeSH
• organokovové sloučeniny MeSH
• osmium tetroxide bispyridine MeSH Prohlížeč
• pyridiny MeSH
• thymin MeSH

The cardiac excitation-contraction coupling is the cellular process through which the heart absolves its blood pumping function, and it is directly affected when cardiac pathologies occur. Cardiomyocytes are the functional units in which this complex biomolecular process takes place: they can be represented as a two-stage electro-chemo and chemo-mechanical transducer, along which each stage can be probed and monitored via appropriate micro/nanotechnology-based tools. Atomic force microscopy (AFM), with its unique nanoresolved force sensitivity and versatile modes of extracting sample properties, can represent a key instrument to study time-dependent heart mechanics and topography at the single cell level. In this work, we show how the integrative possibilities of AFM allowed us to implement an in vitro system which can monitor cardiac electrophysiology, intracellular calcium dynamics, and single cell mechanics. We believe this single cell-sensitive and integrated system will unlock improved, fast, and reliable cardiac in vitro tests in the future.

• Klíčová slova
• Atomic force microscopy, Calcium imaging, Cardiac muscle mechanics, Cardiomyocyte, Electrophysiology, In vitro models,
• MeSH
• analýza dat MeSH
• elektrofyziologické jevy * MeSH
• kardiomyocyty cytologie   fyziologie   MeSH
• mechanické jevy * MeSH
• mikroskopie atomárních sil * přístrojové vybavení   metody   MeSH
• molekulární zobrazování MeSH
• spřažení excitace a kontrakce * MeSH
• vápníková signalizace MeSH
• Publikační typ
• časopisecké články MeSH

Fluidity of lipid membranes is known to play an important role in the functioning of living organisms. The fluorescent probe Laurdan embedded in a lipid membrane is typically used to assess the fluidity state of lipid bilayers by utilizing the sensitivity of Laurdan emission to the properties of its lipid environment. In particular, Laurdan fluorescence is sensitive to gel vs liquid⁻crystalline phases of lipids, which is demonstrated in different emission of the dye in these two phases. Still, the exact mechanism of the environment effects on Laurdan emission is not understood. Herein, we utilize dipalmitoylphosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC) lipid bilayers, which at room temperature represent gel and liquid⁻crystalline phases, respectively. We simulate absorption and emission spectra of Laurdan in both DOPC and DPPC bilayers with quantum chemical and classical molecular dynamics methods. We demonstrate that Laurdan is incorporated in heterogeneous fashion in both DOPC and DPPC bilayers, and that its fluorescence depends on the details of this embedding.

• Klíčová slova
• DFT, Laurdan, TDDFT, classical molecular dynamics, fluorescence,
• MeSH
• 1,2-dipalmitoylfosfatidylcholin chemie   MeSH
• 2-naftylamin analogy a deriváty   chemie   MeSH
• chemické modely * MeSH
• fluorescence MeSH
• fosfatidylcholiny chemie   MeSH
• kvantová teorie MeSH
• laurany chemie   MeSH
• lipidové dvojvrstvy chemie   MeSH
• simulace molekulární dynamiky * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 1,2-dipalmitoylfosfatidylcholin MeSH
• 1,2-oleoylphosphatidylcholine MeSH Prohlížeč
• 2-naftylamin MeSH
• fosfatidylcholiny MeSH
• laurany MeSH
• laurdan MeSH Prohlížeč
• lipidové dvojvrstvy MeSH

Physical mechanisms of phase separation in living systems play key physiological roles and have recently been the focus of intensive studies. The strongly heterogeneous nature of such phenomena poses difficult modeling challenges that require going beyond mean-field approaches based on postulating a free energy landscape. The pathway we take here is to calculate the partition function starting from microscopic interactions by means of cavity methods, based on a tree approximation for the interaction graph. We illustrate them on the binary case and then apply them successfully to ternary systems, in which simpler one-factor approximations are proved inadequate. We demonstrate the agreement with lattice simulations and contrast our theory with coacervation experiments of associative de-mixing of nucleotides and poly-lysine. Different types of evidence are provided to support cavity methods as ideal tools for modeling biomolecular condensation, giving an optimal balance between the consideration of spatial aspects and fast computational results.

• Klíčová slova
• Molecular interaction, Statistical mechanics, Statistical physics,
• Publikační typ
• časopisecké články MeSH

Base stacking is a major interaction shaping up and stabilizing nucleic acids. During the last decades, base stacking has been extensively studied by experimental and theoretical methods. Advanced quantum-chemical calculations clarified that base stacking is a common interaction, which in the first approximation can be described as combination of the three most basic contributions to molecular interactions, namely, electrostatic interaction, London dispersion attraction and short-range repulsion. There is not any specific π-π energy term associated with the delocalized π electrons of the aromatic rings that cannot be described by the mentioned contributions. The base stacking can be rather reasonably approximated by simple molecular simulation methods based on well-calibrated common force fields although the force fields do not include nonadditivity of stacking, anisotropy of dispersion interactions, and some other effects. However, description of stacking association in condensed phase and understanding of the stacking role in biomolecules remain a difficult problem, as the net base stacking forces always act in a complex and context-specific environment. Moreover, the stacking forces are balanced with many other energy contributions. Differences in definition of stacking in experimental and theoretical studies are explained.

• Klíčová slova
• nucleic acids, quantum-chemical calculations, stacking,
• MeSH
• DNA chemie   MeSH
• kvantová teorie MeSH
• molekulární modely MeSH
• RNA * chemie   MeSH
• simulace molekulární dynamiky MeSH
• termodynamika * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA MeSH
• RNA * MeSH

Until now, atomistic simulations of DNA and RNA and their complexes have been executed using well calibrated but conceptually simple pair-additive empirical potentials (force fields). Although such simulations provided many valuable results, it is well established that simple force fields also introduce errors into the description, underlying the need for development of alternative anisotropic, polarizable molecular mechanics (APMM) potentials. One of the most abundant forces in all kinds of nucleic acids topologies is base stacking. Intra- and interstrand stacking is assumed to be the most essential factor affecting local conformational variations of B-DNA. However, stacking also contributes to formation of all kinds of noncanonical nucleic acids structures, such as quadruplexes or folded RNAs. The present study focuses on 14 stacked cytosine (Cyt) dimers and the doubly H-bonded dimer. We evaluate the extent to which an APMM procedure, SIBFA, could account quantitatively for the results of high-level quantum chemistry (QC) on the total interaction energies, and the individual energy contributions and their nonisotropic behaviors. Good agreements are found at both uncorrelated HF and correlated DFT and CCSD(T) levels. Resorting in SIBFA to distributed QC multipoles and to an explicit representation of the lone pairs is essential to respectively account for the anisotropies of the Coulomb and of the exchange-repulsion QC contributions.

• MeSH
• cytosin chemie   MeSH
• dimerizace * MeSH
• DNA chemie   MeSH
• hořčík chemie   MeSH
• kvantová teorie * MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• termodynamika MeSH
• voda chemie   MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytosin MeSH
• DNA MeSH
• hořčík MeSH
• voda MeSH

The mechanical properties of microtubules are of great importance for understanding their biological function and for applications in artificial devices. Although microtubule mechanics has been extensively studied both theoretically and experimentally, the relation to its molecular structure is understood only partially. Here, we report on the structural analysis of microtubule vibration modes calculated by an atomistic approach. Molecular dynamics was applied to refine the atomic structure of a microtubule and a C α elastic network model was analyzed for its normal modes. We mapped fluctuations and local deformations up to the level of individual aminoacid residues. The deformation is mode-shape dependent and principally different in α-tubulins and β-tubulins. Parts of the tubulin dimer sequence responding specifically to longitudinal and radial stress are identified. We show that substantial strain within a microtubule is located both in the regions of contact between adjacent dimers and in the body of tubulins. Our results provide supportive evidence for the generally accepted assumption that the mechanics of microtubules, including its anisotropy, is determined by the bonds between tubulins.

• MeSH
• aminokyseliny chemie   metabolismus   MeSH
• anizotropie MeSH
• konformace proteinů * MeSH
• mechanický stres MeSH
• mikrotubuly chemie   metabolismus   MeSH
• multimerizace proteinu MeSH
• sekvence aminokyselin MeSH
• simulace molekulární dynamiky * MeSH
• tubulin chemie   metabolismus   MeSH
• vibrace MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• tubulin MeSH

Absorption and fluorescence spectra of PRODAN (6-propionyl-2-dimethylaminonaphthalene) were studied by means of the time-dependent density functional theory and the algebraic diagrammatic construction method. The influence of environment, a phosphatidylcholine lipid bilayer and water, was taken into account employing a combination of quantum chemical calculations with empirical force-field molecular dynamics simulations. Additionally, experimental absorption and emission spectra of PRODAN were measured in cyclohexane, water, and lipid vesicles. Both planar and twisted configurations of the first excited state of PRODAN were taken into account. The twisted structure is stabilized in both water and a lipid bilayer, and should be considered as an emitting state in polar environments. Orientation of the excited dye in the lipid bilayer significantly depends on configuration. In the bilayer, the fluorescence spectrum can be regarded as a combination of emission from both planar and twisted structures.

• MeSH
• 2-naftylamin analogy a deriváty   chemie   MeSH
• fluorescenční spektrometrie MeSH
• fosfolipidy chemie   MeSH
• kvantová teorie * MeSH
• lipidové dvojvrstvy chemie   MeSH
• simulace molekulární dynamiky * MeSH
• spektrofotometrie ultrafialová MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• 2-naftylamin MeSH
• fosfolipidy MeSH
• lipidové dvojvrstvy MeSH
• prodan MeSH Prohlížeč

Mechanical properties of DNA are important not only in a wide range of biological processes but also in the emerging field of DNA nanotechnology. We review some of the recent developments in modeling these properties, emphasizing the multiscale nature of the problem. Modern atomic resolution, explicit solvent molecular dynamics simulations have contributed to our understanding of DNA fine structure and conformational polymorphism. These simulations may serve as data sources to parameterize rigid base models which themselves have undergone major development. A consistent buildup of larger entities involving multiple rigid bases enables us to describe DNA at more global scales. Free energy methods to impose large strains on DNA, as well as bead models and other approaches, are also briefly discussed.

• MeSH
• DNA chemie   MeSH
• lidé MeSH
• molekulární konformace MeSH
• molekulární modely * MeSH
• nanotechnologie MeSH
• simulace molekulární dynamiky * MeSH
• systémová biologie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• DNA MeSH

Correlated ab initio as well as semiempirical quantum chemical calculations and molecular dynamics simulations were used to study the intercalation of cationic ethidium, cationic 5-ethyl-6-phenylphenanthridinium and uncharged 3,8-diamino-6-phenylphenanthridine to DNA. The stabilization energy of the cationic intercalators is considerably larger than that of the uncharged one. The dominant energy contribution with all intercalators is represented by dispersion energy. In the case of the cationic intercalators, the electrostatic and charge-transfer terms are also important. The DeltaG of ethidium intercalation to DNA was estimated at -4.5 kcal mol(-1) and this value agrees well with the experimental result. Of six contributions to the final free energy, the interaction energy value is crucial. The intercalation process is governed by the non-covalent stacking (including charge-transfer) interaction while the hydrogen bonding between the ethidium amino groups and the DNA backbone is less important. This is confirmed by the evaluation of the interaction energy as well as by the calculation of the free energy change. The intercalation affects the macroscopic properties of DNA in terms of its flexibility. This explains the easier entry of another intercalator molecule in the vicinity of an existing intercalation site.

• MeSH
• chemické modely * MeSH
• DNA chemie   MeSH
• ethidium chemie   MeSH
• fenantridiny chemie   metabolismus   MeSH
• interkalátory chemie   MeSH
• kationty chemie   MeSH
• konformace nukleové kyseliny MeSH
• kvantová teorie MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• molekulární struktura MeSH
• počítačová simulace MeSH
• termodynamika MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA MeSH
• ethidium MeSH
• fenantridiny MeSH
• interkalátory MeSH
• kationty MeSH