Classical Mechanical Simulations Research Articles

Disulfide bond reduction and exchange in C4 domain of von Willebrand factor undermines platelet binding

BackgroundThe von Willebrand factor (VWF) is a key player in regulating hemostasis through adhesion of platelets to sites of vascular injury. It is a large, multi-domain, mechano-sensitive protein that is stabilized by a net of disulfide bridges. Binding to platelet integrin is achieved by the VWF-C4 domain, which exhibits a fixed fold, even under conditions of severe mechanical stress, but only if critical internal disulfide bonds are closed. ObjectiveTo determine the oxidation state of disulfide bridges in the C4 domain of VWF and implications for VWF’s platelet binding function. MethodsWe combined classical molecular dynamics and quantum mechanical simulations, mass spectrometry, site-directed mutagenesis, and platelet binding assays. ResultsWe show that 2 disulfide bonds in the VWF-C4 domain, namely the 2 major force-bearing ones, are partially reduced in human blood. Reduction leads to pronounced conformational changes within C4 that considerably affect the accessibility of the integrin-binding motif, and thereby impair integrin-mediated platelet binding. We also reveal that reduced species in the C4 domain undergo specific thiol/disulfide exchanges with the remaining disulfide bridges, in a process in which mechanical force may increase the proximity of specific reactant cysteines, further trapping C4 in a state of low integrin-binding propensity. We identify a multitude of redox states in all 6 VWF-C domains, suggesting disulfide bond reduction and swapping to be a general theme. ConclusionsOur data suggests a mechanism in which disulfide bonds dynamically swap cysteine partners and control the interaction of VWF with integrin and potentially other partners, thereby critically influencing its hemostatic function.

Mechanistic Basis for a Connection between the Catalytic Step and Slow Opening Dynamics of Adenylate Kinase.

Escherichia coli adenylate kinase (AdK) is a small, monomeric enzyme that synchronizes the catalytic step with the enzyme's conformational dynamics to optimize a phosphoryl transfer reaction and the subsequent release of the product. Guided by experimental measurements of low catalytic activity in seven single-point mutation AdK variants (K13Q, R36A, R88A, R123A, R156K, R167A, and D158A), we utilized classical mechanical simulations to probe mutant dynamics linked to product release, and quantum mechanical and molecular mechanical calculations to compute a free energy barrier for the catalytic event. The goal was to establish a mechanistic connection between the two activities. Our calculations of the free energy barriers in AdK variants were in line with those from experiments, and conformational dynamics consistently demonstrated an enhanced tendency toward enzyme opening. This indicates that the catalytic residues in the wild-type AdK serve a dual role in this enzyme's function─one to lower the energy barrier for the phosphoryl transfer reaction and another to delay enzyme opening, maintaining it in a catalytically active, closed conformation for long enough to enable the subsequent chemical step. Our study also discovers that while each catalytic residue individually contributes to facilitating the catalysis, R36, R123, R156, R167, and D158 are organized in a tightly coordinated interaction network and collectively modulate AdK's conformational transitions. Unlike the existing notion of product release being rate-limiting, our results suggest a mechanistic interconnection between the chemical step and the enzyme's conformational dynamics acting as the bottleneck of the catalytic process. Our results also suggest that the enzyme's active site has evolved to optimize the chemical reaction step while slowing down the overall opening dynamics of the enzyme.

Machine learning in computational NMR-aided structural elucidation

Structure elucidation is a stage of paramount importance in the discovery of novel compounds because molecular structure determines their physical, chemical and biological properties. Computational prediction of spectroscopic data, mainly NMR, has become a widely used tool to help in such tasks due to its increasing easiness and reliability. However, despite the continuous increment in CPU calculation power, classical quantum mechanics simulations still require a lot of effort. Accordingly, simulations of large or conformationally complex molecules are impractical. In this context, a growing number of research groups have explored the capabilities of machine learning (ML) algorithms in computational NMR prediction. In parallel, important advances have been made in the development of machine learning-inspired methods to correlate the experimental and calculated NMR data to facilitate the structural elucidation process. Here, we have selected some essential papers to review this research area and propose conclusions and future perspectives for the field.

Formation and fragmentation of 2-hydroxyethylhydrazinium nitrate (HEHN) cluster ions: a combined electrospray ionization mass spectrometry, molecular dynamics and reaction potential surface study.

The 2-hydroxyethylhydrazinium nitrate ([HOCH2CH2NH2NH2]+NO3-, HEHN) ionic liquid has the potential to power both electric and chemical thrusters and provide a wider range of specific impulse needs. To characterize its capabilities as an electrospray propellant, we report the formation of HEHN cluster ions in positive electrospray ionization (ESI) and their collision-induced dissociation. The experiment was carried out using ESI guided-ion beam mass spectrometry which mimics an electrospray thruster in terms of ion emission, injection into a vacuum and fragmentation in space. Measurements include compositions of primary ions in the electrospray plume and their individual dissociation product ion cross sections and threshold energies. The results were interpreted in light of theoretical modeling. To determine cluster structures that are comprised of [HE + H]+ and NO3- constituents, classical mechanics simulations were used to create initial guesses; and for clusters that are formed by reactions between ionic constituents, quasi-classical direct dynamics trajectory simulations were used to mimic covalent bond formation and structures. All candidate structures were subject to density functional theory optimization, from which global minimum structures were identified and used for construction of reaction potential energy surface. The comparison between experimental values and calculated dissociation thermodynamics was used to verify the structures for the emitted species [(HEHN)nHE + H]+, [(HEHN)n(HE)2 + H]+, [(HE)n+1 + H]+ and [(HE)nC2H4OH]+ (n = 0-2), of which [(HE)1-2 + H]+ dominates. Due to the protic nature of HEHN, cluster fragmentation can be rationalized by proton transfer-mediated elimination of HNO3, HE and HE·HNO3, and the latter two become dominant in larger clusters. [(HE)2 + H]+ and [(HE)nC2H4OH]+ contain H-bonded water and consequently are featured by water elimination in fragmentation. These findings help to evaluate ion formation and fragmentation efficiencies and their impacts on electrospray propulsion.

Molecular Modelling and Simulations of Light-Harvesting Decanuclear Ru-Based Dendrimers for Artificial Photosynthesis.

The structure of a decanuclear photo‐ and redox‐active dendrimer based on Ru(II) polypyridine subunits, suitable as a light‐harvesting multicomponent species for artificial photosynthesis, has been investigated by means of computer modelling. The compound has the general formula [Ru{(μ‐dpp)Ru[(μ‐dpp)Ru(bpy)2]2}3](PF6)20 (Ru10; bpy=2,2′‐bipyridine; dpp=2,3‐bis(2′‐pyridyl)pyrazine). The stability of possible isomers of each monomer was investigated by performing classical molecular dynamics (MD) and quantum mechanics (QM) simulations on each monomer and comparing the results. The number of stable isomers is reduced to 36 with a prevalence of MER isomerism in the central core, as previously observed by NMR experiments. The simulations on decanuclear dendrimers suggest that the stability of the dendrimer is not linked to the stability of the individual monomers composing the dendrimer but rather governed by the steric constrains originated by the multimetallic assembly. Finally, the self‐aggregation of Ru10 and the distribution of the counterions around the complexes is investigated using Molecular Dynamics both in implicit and explicit acetonitrile solution. In representative examples, with nine and four dendrimers, the calculated pair distribution function for the ruthenium centers suggests a self‐aggregation mechanism in which the dendrimers are approaching in small blocks and then aggregate all together. Scanning transmission electron microscopy complements the investigation, supporting the formation of different aggregates at various concentrations.

Laser-Driven Anharmonic Oscillator: Ground-State Dissociation of the Helium Hydride Molecular Ion by Midinfrared Pulses.

The vibrational motion of molecules represents a fundamental example of an anharmonic oscillator. Using a prototype molecular system, HeH^{+}, we demonstrate that appropriate laser pulses make it possible to drive the nuclear motion in the anharmonic potential of the electronic ground state, increasing its energy above the potential barrier and facilitating dissociation by purely vibrational excitation. We find excellent agreement between the frequency-dependent response of the helium hydride molecular cation to both classical and quantum mechanical simulations, thus removing any ambiguities through electronic excitation. Our results provide access to the rich dynamics of anharmonic quantum oscillator systems and pave the way to state-selective control schemes in ground-state chemistry by the adequate choice of the laser parameters.

Deactivation blocks proton pathways in the mitochondrial complex I

Cellular respiration is powered by membrane-bound redox enzymes that convert chemical energy into an electrochemical proton gradient and drive the energy metabolism. By combining large-scale classical and quantum mechanical simulations with cryo-electron microscopy data, we resolve here molecular details of conformational changes linked to proton pumping in the mammalian complex I. Our data suggest that complex I deactivation blocks water-mediated proton transfer between a membrane-bound quinone site and proton-pumping modules, decoupling the energy-transduction machinery. We identify a putative gating region at the interface between membrane domain subunits ND1 and ND3/ND4L/ND6 that modulates the proton transfer by conformational changes in transmembrane helices and bulky residues. The region is perturbed by mutations linked to human mitochondrial disorders and is suggested to also undergo conformational changes during catalysis of simpler complex I variants that lack the "active"-to-"deactive" transition. Our findings suggest that conformational changes in transmembrane helices modulate the proton transfer dynamics by wetting/dewetting transitions and provide important functional insight into the mammalian respiratory complex I.

Structural preferences of an anti-fouling peptide: From single chain to small molecular assemblies

The structural features of a tripeptide constituted by two different non-coded amino acids, 3,4-dihydroxy-L-phenylalanine (L-DOPA) and 4-fluoro-Phenylalanine, (Phe(4F)), have been investigated by means of classical mechanics simulations. This tripeptide had been characterised as an antifouling agent with great adhesion capabilities. In this work, its conformational preferences have been described in two different environments (gas phase and water solution), at three different pHs and with different degrees of terminal capping. At the same time, the structural dynamics of small aggregates of the tripeptide have been investigated and their ability to stabilise β-sheet based assemblies has been studied. The reported results describe the complexity of the tripeptide conformational preferences due to both the amphiphilic nature of its side chains, and the effect of the ionisation state resulting from the solution conditions. The investigations performed with small tripeptide assemblies in water solution reproduced the previously reported structural features, such as the polymorphism of its aggregates as a function of the pH. At edge pH values, the electrostatic screening imposed by the ions present in the solution facilitates the aggregation of the tripeptide chains, while at neutral pH and low concentrations of ionised species, the polar groups and the hydrogen bond capable groups impose their strength and lead to the disaggregation of the peptide clusters by favouring the solvation of individual chains rather than stabilising the aggregated states.

Failure of molecular dynamics to provide appropriate structures for quantum mechanical description of the aqueous chloride ion charge-transfer-to-solvent ultraviolet spectrum.

The lowest band in the charge-transfer-to-solvent ultraviolet absorption spectrum of aqueous chloride ion is studied by experiment and computation. Interestingly, the experiments indicate that at concentrations up to at least 0.25 M, where calculations indicate ion pairing to be significant, there is no notable effect of ionic strength on the spectrum. The experimental spectra are fitted to aid comparison with computations. Classical molecular dynamic simulations are carried out on dilute aqueous Cl-, Na+, and NaCl, producing radial distribution functions in reasonable agreement with experiment and, for NaCl, clear evidence of ion pairing. Clusters are extracted from the simulations for quantum mechanical excited state calculations. Accurate ab initio coupled-cluster benchmark calculations on a small number of representative clusters are carried out and used to identify and validate an efficient protocol based on time-dependent density functional theory. The latter is used to carry out quantum mechanical calculations on thousands of clusters. The resulting computed spectrum is in excellent agreement with experiment for the peak position, with little influence from ion pairing, but is in qualitative disagreement on the width, being only about half as wide. It is concluded that simulation by classical molecular dynamics fails to provide an adequate variety of structures to explain the experimental CTTS spectrum of aqueous Cl-.

In Silico Structure-Based Repositioning of Approved Drugs for Spike Glycoprotein S2 Domain Fusion Peptide of SARS-CoV-2: Rationale from Molecular Dynamics and Binding Free Energy Calculations.

The membrane-anchored spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a pivotal role in directing the fusion of the virus particle mediated by the host cell receptor angiotensin-converting enzyme 2 (ACE-2). The fusion peptide region of the S protein S2 domain provides SARS-CoV-2 with the biological machinery needed for direct fusion to the host lipid membrane. In our present study, computer-aided drug design strategies were used for the identification of FDA-approved small molecules using the optimal structure of the S2 domain, which exhibits optimal interaction ratios, structural features, and energy variables, which were evaluated based on their performances in molecular docking, molecular dynamics simulations, molecular mechanics/generalized Born model and solvent accessibility binding free energy calculations of molecular dynamics trajectories, and statistical inferences. Among the 2,625 FDA-approved small molecules, chloramphenicol succinate, imipenem, and imidurea turned out to be the molecules that bound the best at the fusion peptide hydrophobic pocket. The principal interactions of the selected molecules suggest that the potential binding site at the fusion peptide region is centralized amid the Lys790, Thr791, Lys795, Asp808, and Gln872 residues.IMPORTANCE The present study provides the structural identification of the viable binding residues of the SARS-CoV-2 S2 fusion peptide region, which holds prime importance in the virus's host cell fusion and entry mechanism. The classical molecular mechanics simulations were set on values that mimic physiological standards for a good approximation of the dynamic behavior of selected drugs in biological systems. The drug molecules screened and analyzed here have relevant antiviral properties, which are reported here and which might hint toward their utilization in the coronavirus disease 2019 (COVID-19) pandemic owing to their attributes of binding to the fusion protein binding region shown in this study.

Classical mechanical simulations of layer- and tunnel-structured manganese oxide minerals

Tecto- and phyllo-manganate minerals serve as important controls in the geochemical cycle of many elements in soils and sediments due to their high surface areas and chemical reactivity. These nanoscale Mn oxides are mainly composed of Mn octahedra in edge- and corner-sharing configurations that produce a range of tunnel and layer structures. Some fundamental aspects of their atomic structures, however, are difficult to characterize unambiguously because of dynamic structural transformations and a wide range of the structural and chemical compositions. Molecular dynamics (MD) simulations based on interatomic pair potentials provide a perspective on nanoscale Mn-oxides that can be inaccessible to experiment or density functional theory (DFT) calculations. We recently introduced a set of interatomic potentials for the atomistic simulation of Mn-oxides (MnFn) that reproduced many of the subtle phyllomanganate structural variations associated with pH, vacancy content, and Mn oxidation state. In this manuscript, we expand the roster of simulated Mn-oxide minerals to include hydrous and anhydrous tunnel structures and δ-MnO2 with octahedral vacancy contents up to 20%. The MnFn potentials reproduced the experimental tectomanganate lattice parameters and interatomic distances to within 5% and the relative energetics of tectomanganates as predicted by a recent DFT study. We also provide new insights into the Mg site occupancy in todorokite and the Zn coordination in vernadite through large-scale atomistic simulations with MnFn that are challenging to simulate with DFT. In the 3 × 3 tunnel structures of todorokite, the central tunnel site is the predominant site for fully-hydrated Mg2+·6H2O with a minority of partially-hydrated Mg2+ cations binding to corner sites at decreased water/cation ratios. The occurrence of tetrahedral Zn complexes is dependent upon not only the Mn(IV) vacancy content but also the layer spacing and sheet registry. These atomistic simulation results demonstrate the ability of the MnFn potentials to reproduce the basic structures of nanophase Mn-oxides and the capability to perform large-scale modeling that is required to address the subtle structural variations associated with changes in environmental conditions.

Ultralarge Modulation of Fluorescence by Neuromodulators in Carbon Nanotubes Functionalized with Self-Assembled Oligonucleotide Rings.

Noncovalent interactions between single-stranded DNA (ssDNA) oligonucleotides and single wall carbon nanotubes (SWNTs) have provided a unique class of tunable chemistries for a variety of applications. However, mechanistic insight into both the photophysical and intermolecular phenomena underlying their utility is lacking, which results in obligate heuristic approaches for producing ssDNA-SWNT based technologies. In this work, we present an ultrasensitive "turn-on" nanosensor for neuromodulators dopamine and norepinephrine with strong relative change in fluorescence intensity (Δ F/ F0) of up to 3500%, a signal appropriate for in vivo neuroimaging, and uncover the photophysical principles and intermolecular interactions that govern the molecular recognition and fluorescence modulation of this nanosensor synthesized from the spontaneous self-assembly of (GT)6 ssDNA rings on SWNTs. The fluorescence modulation of the ssDNA-SWNT conjugate is shown to exhibit remarkable sensitivity to the ssDNA sequence chemistry, length, and surface density, providing a set of parameters with which to tune nanosensor dynamic range, analyte selectivityand strength of fluorescence turn-on. We employ classical and quantum mechanical molecular dynamics simulations to rationalize our experimental findings. Calculations show that (GT)6 ssDNA form ordered rings around (9,4)SWNTs, inducing periodic surface potentials that modulate exciton recombination lifetimes. Further evidence is presented to elucidate how dopamine analyte binding modulates SWNT fluorescence. We discuss the implications of our findings for SWNT-based molecular imaging applications.

Unravelling the GLY-PRO-GLU tripeptide induced reconstruction of the Au(110) surface at the molecular scale

The adsorption of GLY-PRO-GLU tripeptide on Au(110) is investigated within the frame of all atom classical mechanics simulations and Density Functional Theory, focusing on the surface reconstruction. It is shown that the tripeptide adsorption reorganizes and restructures the Au(110) surface. A mechanism for the surface restructuration is proposed for both the neutral and zwitterionic form of the peptide at room temperature in Ultra High Vacuum. Diverse residues may be involved in the Au atoms displacement, and in particular glutamic acid, triggering a double proton transfer and the formation of a zwitter ionic state, is found to be responsible for the triggering of the surface reconstruction.

The symmetrical quasi-classical approach to electronically nonadiabatic dynamics applied to ultrafast exciton migration processes in semiconducting polymers.

In the last several years, a symmetrical quasi-classical (SQC) windowing model applied to the classical Meyer-Miller (MM) vibronic Hamiltonian has been shown to be a simple, efficient, general, and quite-accurate method for treating electronically nonadiabatic processes at the totally classical level. Here, the SQC/MM methodology is applied to ultrafast exciton dynamics in a Frenkel/site-exciton model of oligothiophene (OT) as a model of organic semiconductor polymers. In order to keep the electronic representation as compact and efficient as possible, the adiabatic version of the MM Hamiltonian was employed, with dynamical calculations carried out in the recently developed "kinematic momentum" representation, from which site/monomer-specific (diabatic) excitation probabilities were extracted using a new procedure developed in this work. The SQC/MM simulation results are seen to describe coherent exciton transport driven by planarization of a central torsion defect in the OT oligomer as well as to capture exciton self-trapping effects in good agreement with benchmark quantum calculations using the multi-layer multiconfiguration time-dependent Hartree approach. The SQC/MM calculations are also seen to significantly outperform the standard Ehrenfest approach, which shows serious discrepancies. These results are encouraging, not only because they illustrate a significant further application of the SQC/MM approach and its utility, but because they strongly suggest that classical mechanical simulations (with the potential for linear scaling efficiency) can be used to capture, quantitatively, important dynamical features of electronic excitation energy transfer in semiconducting polymers.

Molecular simulations of hydrated phyllomanganates

Hydrated phyllomanganates are layered Mn-oxide minerals with interlayers that can possess variable water contents and react strongly with trace metals due to octahedral vacancies in the layer. The unique properties of phyllomanganates afford them a significant role in many environmental phenomena that affect soil and water composition mainly via cation exchange and adsorption of trace metals. Slight variations in the structural and chemical composition often result in a dramatic difference in the chemical reactivity of the minerals. Molecular simulations at the classical mechanical level of theory, which uses a simplified description of the interatomic potential energies, can provide an atomistic perspective of the relationship between the chemical composition and the bulk and interlayer structures. We introduce a set of interatomic potentials for hydrated phyllomanganates with variable vacancy and Mn3+ content and report the classical mechanical simulation results performed at standard temperature and pressure. The potentials we introduce provide not only a reasonable reproduction of the experimentally determined atomic structures of the chalcophanite group, but also new insights on similar phyllomanganate minerals with hexagonal symmetry and a range of vacancy contents. When a vacancy is protonated, Mn3+ is unstable in the hexagonal birnessite layer and occupies the interlayer as a cap on the associated vacancy. When a vacancy was charge-balanced by Mn3+ and Na+, considerable amounts of Mn3+ were incorporated into the hexagonal birnessite layer, but only at total Mn(III) contents greater than ∼10% and with disordered layer stacking. The potentials also predicted a vacancy-free, triclinic Na-birnessite structure with Mn(III)-rich rows in the layer which were arranged parallel to the b-axis and separated by two rows of Mn(IV) octahedra. The dominant interlayer Na complex at a water content ≥0.7 H2O/MnO2 was an octahedrally-coordinated, split interlayer site with two birnessite O atoms in the axial positions and four interlayer H2O in the equatorial positions. Other interlayer Na complexes including some edge- and face-sharing complexes existed in trace amounts (<10%). These classical mechanical simulations represent a successful first test of the introduced interatomic potentials, which can be used to further explore the interlayer and surface complexes of phyllomanganate and birnessite-group minerals.

Retinal isomerization and water-pore formation in channelrhodopsin-2

Channelrhodopsin-2 (ChR2) is a light-sensitive ion channel widely used in optogenetics. Photoactivation triggers a trans-to-cis isomerization of a covalently bound retinal. Ensuing conformational changes open a cation-selective channel. We explore the structural dynamics in the early photocycle leading to channel opening by classical (MM) and quantum mechanical (QM) molecular simulations. With QM/MM simulations, we generated a protein-adapted force field for the retinal chromophore, which we validated against absorption spectra. In a 4-µs MM simulation of a dark-adapted ChR2 dimer, water entered the vestibules of the closed channel. Retinal all-trans to 13-cis isomerization, simulated with metadynamics, triggered a major restructuring of the charge cluster forming the channel gate. On a microsecond time scale, water penetrated the gate to form a membrane-spanning preopen pore between helices H1, H2, H3, and H7. This influx of water into an ion-impermeable preopen pore is consistent with time-resolved infrared spectroscopy and electrophysiology experiments. In the retinal 13-cis state, D253 emerged as the proton acceptor of the Schiff base. Upon proton transfer from the Schiff base to D253, modeled by QM/MM simulations, we obtained an early-M/P2390-like intermediate. Rapid rotation of the unprotonated Schiff base toward the cytosolic side effectively prevents its reprotonation from the extracellular side. From MM and QM simulations, we gained detailed insight into the mechanism of ChR2 photoactivation and early events in pore formation. By rearranging the network of charges and hydrogen bonds forming the gate, water emerges as a key player in light-driven ChR2 channel opening.

Multiscale Study of Plasmonic Scattering and Light Trapping Effect in Silicon Nanowire Array Solar Cells.

Nanometallic structures that support surface plasmons provide new ways to confine light at deep-subwavelength scales. The effect of light scattering in nanowire array solar cells is studied by a multiscale approach combining classical electromagnetic (EM) and quantum mechanical simulations. A photovoltaic device is constructed by integrating a silicon nanowire array with a plasmonic silver nanosphere. The light scatterings by plasmonic element and nanowire array are obtained via classical EM simulations, while current-voltage characteristics and optical properties of the nanowire cells are evaluated quantum mechanically. We found that the power conversion efficiency (PCE) of photovoltaic device is substantially improved due to the local field enhancement of the plasmonic effect and light trapping by the nanowire array. In addition, we showed that there exists an optimal nanowire number density in terms of optical confinement and solar cell PCE.

Bond breaking in epoxy systems: A combined QM/MM approach.

A novel method to combine quantum mechanics (QM) and molecular mechanics has been developed to accurately and efficiently account for covalent bond breaking in polymer systems under high strain without the use of predetermined break locations. Use of this method will provide a better fundamental understanding of the mechano-chemical origins of fracture in thermosets. Since classical force fields cannot accurately account for bond breaking, and QM is too demanding to simulate large systems, a hybrid approach is required. In the method presented here, strain is applied to the system using a classical force field, and all bond lengths are monitored. When a bond is stretched past a threshold value, a zone surrounding the bond is used in a QM energy minimization to determine which, if any, bonds break. The QM results are then used to reconstitute the system to continue the classical simulation at progressively larger strain until another QM calculation is triggered. In this way, a QM calculation is only computed when and where needed, allowing for efficient simulations. A robust QM method for energy minimization has been determined, as well as appropriate values for the QM zone size and the threshold bond length. Compute times do not differ dramatically from classical molecular mechanical simulations.

Molecular Dynamics Simulations of Pyrophyllite Edge Surfaces: Structure, Surface Energies, and Solvent Accessibility

AbstractAtomistic simulations of 2:1 clay minerals based on parameterized forcefields have been applied successfully to provide a detailed description of the interfacial structure and dynamics of basal planes and interlayers, but have made limited progress in exploring the edge surfaces of these ubiquitous layer-type aluminosilicates. In the present study, molecular dynamics simulations and energy-minimization calculations of the edge surfaces using the fully flexible CLAYFF forcefield are reported. Pyrophyllite provides an ideal prototype for the 2:1 clay-mineral edge surface because it possesses no structural charge, thus rendering the basal planes inert, while crystal-growth theory can be applied to identify two major candidates for the structure of the edge surfaces. Models based on these candidate structures reproduced bulk crystal bond distances accurately when compared to X-ray data and ab initio molecular simulations, and the predicted edge surface bond distances were in agreement with those determined via ab initio simulation. The calculated surface free energy and surface stress led to an accurate prediction of pyrophyllite nanoparticle morphology, while surface excess energies calculated for the edge surfaces were always negative. These results are consistent with the observed pyrophyllite nanoparticle morphology, with the concept of negative interfacial energies, and conditions that may give rise to them including a role in the stabilization of layer-type nanoparticulate minerals. Molecular dynamics simulations of hydrated nanoparticle edge surfaces indicated five reactive surface oxygen sites on the dominant candidate edge, in agreement with a recent model of proton titration data for 2:1 clay minerals. These promising results illustrate the potential for classical mechanical atomistic simulations that explore edge surface phenomena at much greater length- and times-scales than are currently possible with computationally expensive ab initio methods.

Investigation of the Ergopeptide Epimerization Process

Ergopeptides, like ergocornine and a-ergocryptine, exist in an S- and in an R-configuration. Kinetic experiments imply that certain configurations are preferred depending on the solvent. The experimental methods are explained in this article. Furthermore, computational methods are used to understand this configurational preference. Standard quantum chemical methods can predict the favored configurations by using minimum energy calculations on the potential energy landscape. However, the explicit role of the solvent is not revealed by this type of methods. In order to better understand its influence, classical mechanical molecular simulations are applied. It appears from our research that “folding” the ergopeptide molecules into an intermediate state (between the S- and the R-configuration) is mechanically hindered for the preferred configurations.