Aggregation of amyloid-
β
(Aβ) peptides, cleaved from the amyloid precursor protein, is known as a precursor of the Alzheimer’s disease (AD). It is also known that Alzheimer’s disease is ...characterized by a substantial decrease of the amount of polyunsaturated lipids in the neuronal membranes of the frontal gray matter. To get insight into possible interconnection of these phenomena, we have carried out molecular dynamics simulations of two fragments of A
β
peptide, A
β
1
-
28
and A
β
26
-
40
, in four different lipid bilayers: two monocomponent ones (14:0-14:0 PC, 18:0-22:6 PC), and two bilayers containing mixtures of 18:0-18:0 PE, 22:6-22:6 PE, 16:0-16:0 PC and 18:1-18:1 PC lipids of composition mimicking neuronal membranes in a “healthy” and “AD” brain. The simulations showed that the presence of lipids with highly unsaturated 22:6
cis
fatty acids chains strongly affects the interaction of amyloid-
β
peptides with lipid membranes. The polyunsaturated lipids cause stronger adsorption of A
β
-peptides by the membrane and lead to weaker binding between peptides when the latter form aggregates. This difference in the behaviour observed in monocomponent bilayers is propagated in a similar fashion to the mixed membranes mimicking composition of neuronal membranes in “healthy” and “AD” brains, with “healthy” membrane having higher fraction of polyunsaturated lipids. Our simulations give strong indication that it can be physical–chemical background of the interconnection between amyloid fibrillization causing Alzheimer’s disease, and content of polyunsaturated lipids in the neuronal membranes.
A more efficient version of the Expanded Ensembles method for calculation of free energy in molecular‐mechanical simulations is proposed. The method is based on the Horowitz L2MC approach to ...accelerate movement along the “alchemical” coordinate. It is possible to achieve the same efficiency of the algorithm both with the optimal number of “windows” and with a larger number of them compared to the original algorithm. Since the optimal number of windows is unknown a priory, the proposed algorithm is more robust than the traditional one. We can choose the number of windows in excess and do not worry about the loss of efficiency. We illustrate the method's efficiency with the computation of the hydration free energies of pyridine and water.
A more effective version of the Expanded Ensembles method for calculation of Free Energy in molecular‐mechanical calculations is proposed. It is possible to achieve the same efficiency of the algorithm both with the optimal number of the “alchemical” coordinate “windows” and with a larger number of them compared to the original algorithm. Since a priory the optimal number of windows is not known the algorithm is more robust than traditional one.
Due to the vast length scale inside the cell nucleus, multiscale models are required to understand chromatin folding, structure, and dynamics and how they regulate genomic activities such as DNA ...transcription, replication, and repair. We study the interactions and structure of condensed phases formed by the universal building block of chromatin, the nucleosome core particle (NCP), using bottom-up multiscale coarse-grained (CG) simulations with a model extracted from all-atom MD simulations. In the presence of the multivalent cations Mg(H2O)62+ or CoHex3+, we analyze the internal structures of the NCP aggregates and the contributions of histone tails and ions to the aggregation patterns. We then derive a "super" coarse-grained (SCG) NCP model to study the macroscopic scale phase separation of NCPs. The SCG simulations show the formation of NCP aggregates with Mg(H2O)62+ concentration-dependent densities and sizes. Variation of the CoHex3+ concentrations results in highly ordered lamellocolumnar and hexagonal columnar phases in agreement with experimental data. The results give detailed insights into nucleosome interactions and for understanding chromatin folding in the cell nucleus.
The use of carbon-based nanomaterials is tremendously increasing in various areas of technological, bioengineering, and biomedical applications. The functionality of carbon-based nanomaterials can be ...further broadened
chemical functionalization of carbon nanomaterial surfaces. On the other hand, concern is rising on possible adverse effects when nanomaterials are taken up by biological organisms. In order to contribute into understanding of interactions of carbon-based nanomaterials with biological matter, we have investigated adsorption of small biomolecules on nanomaterials using enhanced sampling molecular dynamics. The biomolecules included amino acid side chain analogues, fragments of lipids, and sugar monomers. The adsorption behavior on unstructured amorphous carbon, pristine graphene and its derivatives (such as few-layer graphene, graphene oxide, and reduced graphene oxide) as well as pristine carbon nanotubes, and those functionalized with OH
, COOH
, COO
, NH
, and NH
groups was investigated with respect to surface concentration. An adsorption profile, that is, the free energy as a function of distance from the nanomaterial surfaces, was determined for each molecule and surface using the Metadynamics approach. The results were analyzed in terms of chemical specificity, surface charge, and surface concentration. It was shown that although morphology of the nanomaterial has a limited effect on the adsorption properties, functionalization of the surface by various molecular groups can drastically change the adsorption behavior that can be used in the design of nanosurfaces with highly selective adsorption properties and safe for human health and environment.
We present software package MagiC, which is designed to perform systematic structure-based coarse graining of molecular models. The effective pairwise potentials between coarse-grained sites of ...low-resolution molecular models are constructed to reproduce structural distribution functions obtained from the modeling of the system in a high resolution (atomistic) description. The software supports coarse-grained tabulated intramolecular bond and angle interactions, as well as tabulated nonbonded interactions between different site types in the coarse-grained system, with the treatment of long-range electrostatic forces by the Ewald summation. Two methods of effective potential refinement are implemented: iterative Boltzmann inversion and inverse Monte Carlo, the latter accounting for cross-correlations between pair interactions. MagiC uses its own Metropolis Monte Carlo sampling engine, allowing parallel simulation of many copies of the system with subsequent averaging of the properties, which provides fast convergence of the method with nearly linear scaling at parallel execution.
In this work, we present results from molecular dynamics simulations of aqueous solutions of furfural and 5-hydroxymethylfurfural, which are important intermediates in the hydrothermal carbonization ...processes of biomass conversion. The computations were performed both at ambient and hydrothermal conditions using a two-level factorial design varying concentration, temperature, and pressure. A number of equilibrium and dynamic properties have been computed including enthalpies and free energies of vaporization, free energies of solvation, diffusion coefficients, and rotational/reorientational correlation times. Structural properties of solutions were analyzed using radial and spatial distribution functions. It was shown that the formation of hydrogen bonds among 5-hydroxymethylfurfural molecules is preferred compared to hydrogen bonding between 5-hydroxymethylfurfural and water. In addition, our results suggest that the oxygen atoms in the furan rings of furfural and 5-hydroxymethylfurfural do not participate in hydrogen bonding to the same extent as the oxygen atoms in the hydroxyl and carbonyl groups. It is also observed that furfural molecules aggregate under certain conditions, and we show how this is affected by changes in temperature, pressure, and concentration in agreement with experimental solubility data. The analysis of the computational results provides useful insight into the structure and dynamics of the considered molecules at conditions of hydrothermal carbonization, as well as at ambient conditions.
DNA condensation and phase separation is of utmost importance for DNA packing in vivo with important applications in medicine, biotechnology and polymer physics. The presence of hexagonally ordered ...DNA is observed in virus capsids, sperm heads and in dinoflagellates. Rigorous modelling of this process in all-atom MD simulations is presently difficult to achieve due to size and time scale limitations. We used a hierarchical approach for systematic multiscale coarse-grained (CG) simulations of DNA phase separation induced by the three-valent cobalt(III)-hexammine (CoHex3+). Solvent-mediated effective potentials for a CG model of DNA were extracted from all-atom MD simulations. Simulations of several hundred 100-bp-long CG DNA oligonucleotides in the presence of explicit CoHex3+ ions demonstrated aggregation to a liquid crystalline hexagonally ordered phase. Following further coarse-graining and extraction of effective potentials, we conducted modelling at mesoscale level. In agreement with electron microscopy observations, simulations of an 10.2-kb-long DNA molecule showed phase separation to either a toroid or a fibre with distinct hexagonal DNA packing. The mechanism of toroid formation is analysed in detail. The approach used here is based only on the underlying all-atom force field and uses no adjustable parameters and may be generalised to modelling chromatin up to chromosome size.
The nucleosome core particle (NCP) is a large complex of 145–147 base pairs of DNA and eight histone proteins and is the basic building block of chromatin that forms the chromosomes. Here, we develop ...a coarse-grained (CG) model of the NCP derived through a systematic bottom-up approach based on underlying all-atom MD simulations to compute the necessary CG interactions. The model produces excellent agreement with known structural features of the NCP and gives a realistic description of the nucleosome–nucleosome attraction in the presence of multivalent cations (Mg(H2O)6 2+ or Co(NH3)6 3+) for systems comprising 20 NCPs. The results of the simulations reveal structural details of the NCP–NCP interactions unavailable from experimental approaches, and this model opens the prospect for the rigorous modeling of chromatin fibers.
Piezoelectric semiconductors have emerged as redox catalysts, and challenges include effective conversion of mechanical energy to piezoelectric polarization and achieving high catalytic activity. The ...catalytic activity can be enhanced by simultaneous irradiation of ultrasound and light, but the existing piezoelectric semiconductors have trouble absorbing visible light. A piezoelectric catalyst is designed and tested for the generation of hydrogen peroxide (H2O2). It is based on Nb‐doped tetragonal BaTiO3 (BaTiO3:Nb) and is sensitized by carbon quantum dots (CDs). The photosensitizer injects electrons into the conduction band of the semiconductor, while the piezoelectric polarization directed electrons to the semiconductor surface, allowing for a high‐rate generation of H2O2. The piezoelectric polarization field restricts the recombination of photoinduced electron–hole pairs. A production rate of 1360 µmol gcatalyst−1 h−1 of H2O2 is achieved under visible light and ultrasound co‐irradiation. Individual piezo‐ and photocatalysis yielded lower production rates. Furthermore, the CDs enhance the piezocatalytic activity of the BaTiO3:Nb. It is noted that moderating the piezoelectricity of BaTiO3:Nb via microstructure modulation influences the piezophotocatalytic activity. This work shows a new methodology for synthesizing H2O2 by using visible light and mechanical energy.
Carbon quantum dots sensitized Nb‐doped tetragonal BaTiO3 nanopiezoelectrics are considerably effective in simultaneously utilizing visible light and vibration energy, thus achieving high hydrogen peroxide yields from ethanol and water suspensions. This is because the sensitized piezoelectrics‐mediated polarization field accelerates the migration of photoinduced charge carriers.
Nanomaterials possess a wide range of potential applications due to their novel properties and exceptionally high activity as a result of their large surface to volume ratios compared to bulk matter. ...The active surface may present both advantage and risk when the nanomaterials interact with living organisms. As the overall biological impact of nanomaterials is triggered and mediated by interactions at the bio-nano interface, an ability to predict those from the atomistic descriptors, especially before the material is produced, can present enormous advantage for the development of nanotechnology. Fast screening of nanomaterials and their variations for specific biological effects can be enabled using computational materials modelling. The challenge lies in the range of scales that needs to be crossed from the material-specific atomistic representation to the relevant length scales covering typical biomolecules (proteins and lipids). In this work, we present a systematic multiscale approach that allows one to evaluate crucial interactions at the bionano interface from the first principles without any prior information about the material and thus establish links between the details of the nanomaterials structure to protein-nanoparticle interactions. As an example, an advanced computational characterization of titanium dioxide nanoparticles (6 different surfaces of rutile and anatase polymorphs) has been performed. We computed characteristics of the titanium dioxide interface with water using density functional theory for electronic density, used these parameters to derive an atomistic force field, and calculated adsorption energies for essential biomolecules on the surface of titania nanoparticles
via
direct atomistic simulations and coarse-grained molecular dynamics. Hydration energies, as well as adsorption energies for a set of 40 blood proteins are reported.
We present a multiscale computational approach for the first-principles study of bio-nano interactions. Using titanium dioxide as a case study, we evaluate the affinity of titania nanoparticles to water and biomolecules through atomistic and coarse-grained techniques.
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