290 research outputs found
Exploration, representation and rationalization of the conformational phase-space of N-glycans
No full textCollection of structure and trajectory files of free N-glycans simulated in solution using either the CHARMM36m or GLYCAM06j force field. Simulations are either plain MD or enhanced sampled via the combination of replica exchange methods REST-RECT
Accuracy of buffered-force QM/MM simulations of silica
No full textWe report comparisons between energy-based quantum mechanics/molecular mechanics (QM/MM) and buffered force-based QM/MM simulations in silica. Local quantities—such as density of states, charges, forces, and geometries—calculated with both QM/MM approaches are compared to the results of full QM simulations. We find the length scale over which forces computed using a finite QM region converge to reference values obtained in full quantum-mechanical calculations is ∼10 Å rather than the ∼5 Å previously reported for covalent materials such as silicon. Electrostatic embedding of the QM region in the surrounding classical point charges gives only a minor contribution to the force convergence. While the energy-based approach provides accurate results in geometry optimizations of point defects, we find that the removal of large force errors at the QM/MM boundary provided by the buffered force-based scheme is necessary for accurate constrained geometry optimizations where Si–O bonds are elongated and for finite-temperature molecular dynamics simulations of crack propagation. Moreover, the buffered approach allows for more flexibility, since special-purpose QM/MM coupling terms that link QM and MM atoms are not required and the region that is treated at the QM level can be adaptively redefined during the course of a dynamical simulation
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Lessons from a challenging system: accurate adsorption free energies at the amino acid/ZnO interface
No full textWe undertake steps to overcome four challenges that have hindered the understanding of ZnO/biomolecule interfaces at the atomic scale; parametrization of a classical force field, ZnO surface termination and amino acid protonation state in methanol, and convergence of enhanced- sampling molecular dynamics simulations. We predict adsorption free energies for histidine, serine, cysteine and tryptophan in remarkable agreement with experimental measurements obtained via a novel indicator-displacement assay. Adsorption is driven by direct surface/amino-acid interactions mediated by terminal hydroxyl groups and stabilized by strongly-structured methanol solvation shells
Tidying up the conformational ensemble of a disordered peptide by computational prediction of spectroscopic fingerprints
No full textThe most advanced structure prediction methods are powerless in exploring the conformational ensemble of disordered peptides and proteins and for this reason the "protein folding problem" remains unsolved. We present a novel methodology that enables the accurate prediction of spectroscopic fingerprints (circular dichroism, infrared, Raman, and Raman optical activity), and by this allows for "tidying up" the conformational ensembles of disordered peptides and disordered regions in proteins. This concept is elaborated for and applied to a dodecapeptide, whose spectroscopic fingerprint is measured and theoretically predicted by means of enhanced-sampling molecular dynamics coupled with quantum mechanical calculations. Following this approach, we demonstrate that peptides lacking a clear propensity for ordered secondary-structure motifs are not randomly, but only conditionally disordered. This means that their conformational landscape, or phase-space, can be well represented by a basis-set of conformers including about 10 to 100 structures. The implications of this finding have profound consequences both for the interpretation of experimental electronic and vibrational spectral features of peptides in solution and for the theoretical prediction of these features using accurate and computationally expensive techniques. The here-derived methods and conclusions are expected to fundamentally impact the rationalization of so-far elusive structure-spectra relationships for disordered peptides and proteins, towards improved and versatile structure prediction methods
Molecular Dynamics Simulations of the Silica–Cell Membrane Interaction: Insights on Biomineralization and Nanotoxicity
No full textThe interaction of
silica (SiO2) with biological systems
is complex and contradictory. On the one hand, silica is at the basis
of several biomineralization processes (e.g., in sponges). On the
other hand, silica nanoparticles and dust may lead to silicosis and,
at the cellular level, hemolysis. These toxic responses are strongly
dependent on the silica polymorph and their root causes are still
under debate. Both silica biomineralization and silica-induced nanotoxicity
could be related to similar mechanisms of molecular recognition between
the cellular membranes and the surface of the SiO2 particles.
On the basis of this hypothesis, we employed classical molecular dynamics
simulations, coupled to advanced sampling techniques, to achieve an
atomistic picture of the interactions between different types of silica
nanoparticles and the membrane of erythrocytes. Our predicted free-energy
profiles associated with membrane crossing give no evidence for segregation
of nanoparticles at the membrane/water interface, irrespective of
their Si nuclearity, structure, and charge. The associated molecular
trajectories, however, are suggestive of a possible direct translocation
mechanism, in which silica nanoclusters elicit both local and large-scale
effects on the membrane dynamics and stability. This gives hints on
possible pathways for silica nanotoxicity based on nanoparticle-induced
membrane perforation
Atomistic details of chymotrypsin conformational changes upon adsorption on silica
No full textAdsorption of enzymes on solid surfaces may lead to conformational changes that reduce their catalytic conversion activity and are thus detrimental to the efficiency of biotechnology or biosensing applications. This work is a joint theoretical and experimental endeavor in which we identify and quantify the conformational changes that chymotrypsin undergoes when in contact with the surface of amorphous silica nanoparticles. For this purpose, we use circular dichroism spectroscopy, standard molecular dynamics and advanced-sampling methods. Only the combination of these techniques allowed us to pinpoint a destabilization effect of silica on specific structural motifs of chymotrypsin. They are linked by the possibility of theoretically predicting CD spectra, allowing us to elucidate the source of the experimentally observed spectral changes. We find that chymotrypsin loses part of its helical content upon adsorption, with minor perturbation of its overall tertiary structure, associated to changes in the aromatic interactions. We demonstrate that the C-terminal helical fragment is unfolded as an isolated oligopeptide in pure water, folded as an α-helix as terminus of chymotrypsin in solution, and again partly disordered when the protein is adsorbed on silica. We believe that the joint methodology introduced in this manuscript has a direct general applicability to investigate any biomolecule - inorganic surface system. Methods to theoretically predict Circular Dichroism spectra from atomistic simulations were compared and improved. The drawbacks of the approaches are discussed; in particular the limited capability of advanced-sampling MD schemes to explore the conformational phase space of large proteins, and the dependency of the predicted ellipticity bands on the choice of calculation parameters.Keywords: Protein adsorption, Silica, Circular dichroism, Molecular dynamics, Free energy, Conformational change
Bindungsaffinitäten und -phänomene an der Grenzfläche zwischen Peptiden und Zinkoxid
No full textPeptide sequences can selectively bind to inorganic substrates in a process similar to the concept of molecular recognition. Here we focused on zinc oxide as an important representative of functional oxides and identified binding peptides with an affinity for different ZnO facets. Five peptides were selected and their conformational ensemble (macrostate) and sensitivity to adsorption were characterised via circular dichroism (CD) spectroscopy. The microstates within their conformational ensembles are accessed by enhanced sampling simulations. To quantify the free energies of adsorption, an optically sectioned indicator displacement assay (O-IDA) was adapted to the peptide/ZnO interface and compared to the results of single molecule force spectroscopy (SMFS), leading to a good agreement between the two approaches
Molekulardynamische Simulationen des Proteinadsorptionsprozesses auf Oxiden
No full textThe adsorption of chymotrypsin and lysozyme on amorphous silica and titania is studied by molecular dynamics (MD) simulations in comparison to experiments. The simulations allow an atomistic view of the adsorption process including long-range interactions, multi-protein effects, contact analysis and surface-induced conformational changes. The surface contact stability is investigated by Steered MD simulations and Atomic Force Spectroscopy experiments. Surface-induced conformational changes are studied by classical and further developed free energy MD methods based on Metadynamics, Replica Exchange Solute Tempering and Umbrella sampling and are compared to circular dichroism experiments. The protein orientation is highly influenced by its dipole moment whereas protein binding motifs are formed mainly by positively charged amino acids. The comparison to the experiment shows that protein-protein interactions and the hydration shell of oxide and protein need to be considered as well
Molekular dynamische Simulationen von ZnO: Eine schrittweise Annäherung an ein detailliertes Verständnis der komplexen fest/flüssig/bio Grenzfläche
No full textThis thesis was set out to theoretically investigate the complex ZnO/water/bio interface. In this work I have presented results using a step-by-step approach, comprising different model systems, which aimed to depict various aspects of this complex surface, starting from the primitive cell of bulk ZnO, going to a slab model including a surface charge in contact with a pentapeptide. One of the main focus points in all the different model systems was thereby the interaction between the inorganic surface and water and how a water environment changes the adsorption characteristics of approaching molecules. This is an aspect that has until today only been considered by a few theoretical studies focusing on ZnO. Nevertheless the results presented in this work prove that its influence is of tremendous importance for many systems
Theoretische Untersuchung lumineszierender Defekte im Diamant
No full textThe nitrogen-vacancy (NV) color center in diamond has attracted a lot of attention during the past few years. Its strong room temperature luminescence can be utilized in single photon emitters for quantum cryptography, and for optical labeling in biomedical imaging. All applications critically rely on thermodynamically and optically stable defects, introduced in sufficient concentration and suitable charge state. To clarify the conditions for that, I have performed theoretical calculations for bulk crystals, slabs and nanoclusters of diamond. I will show that the concentration of NV centers can be enhanced by increasing the irradiation flux and by using higher annealing temperatures, to annihilate divacancies. Most applications require NV(-) centers very close to the surface, which can affect the luminescence of the center, leading to undesired blinking effects or even bleaching. This also happens in nanodiamonds, where band- bending effects cannot be invoked for explanation. Therefore, I have investigated the interaction of surface states in variously terminated diamond slabs with the NV(-) center. I have identified a combination of surface terminators with no effect on the luminescence of this defect. Such a termination can be realized by mild oxidation of hydrogenated surfaces or by oxidation with acids
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