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- Physik (4379) (remove)
Neutron stars are unique laboratories for the investigation of the high density properties of bulk matter. In this work, the astrophysical constraints for a phase transition from hadronic matter to deconfined quark matter are examined thoroughly. A scheme for relating known astrophysical observables such as mass, radius and tidal deformability to the parameter space of such a transition is devised and applied to the set of data currently available.
In order to span a wide parameter space, a highly parameterizable relativistic mean field equation in compliance with chiral effective field theory results is used, where the stiffness of the equation of state can be varied via the effective mass at saturation density. The phase transitions are modelled using a Maxwell construction and assumed to be of first order, with a constant speed of sound quark matter model. The resulting equations of state are analyzed and divided into four categories, which can be used to constrain the parameter space that allows phase transition. It is highlighted, that a subset of this parameter space would even be detectable without the need of higher precision measurements. A phase transition at high densities is shown to be particularly promising in this regard. Finally, the groundwork is laid to apply the equation of state used in this work for supernova or merger simulations, by extending it to non-zero temperatures.
Die Wirkungsweise des Protonen-Wendellinearbeschleunigers und sein prinzipieller Aufbau werden kurz beschrieben und Angaben über die erreichbare Parallelimpedanz gemacht. Es wird gezeigt, wie durch sektionsweisen Aufbau eine variable Endenergie erzielt und die Kühl- und Fokussierprobleme gelöst werden können. Zwei Konstruktionsbeispiele für kontinuierlichen und gepulsten Betrieb werden näher ausgeführt.
Light-particle accompanied fission is expected to yield results from which one hopes to learn more about binary scission configurations. As a step in this direction, we present a model that allows the calculation of the probabilities with which a given three-particle setup follows from different binary configurations. First results show the workability of the model.
Über das Absorptionsverhalten verschiedener Quarzglassorten im Spektralbereich von 150 μ bis 275 μ
(1961)
Die Fermi-Verteilung gibt die Verteilung von Elektronen über die verschiedenen Energieniveaus in einem Festkörper unter der Voraussetzung an, daß sich ein thermodynamischer Gleichgewichtszustand eingestellt hat. Bei der Untersuchung von Leitfähigkeitsproblemen werden geringfügige Störungen dieser Gleichgewichtsverteilung durch elektrische Felder, Temperaturgefälle u. dgl. berücksichtigt. Der innere Photoeffekt bewirkt eine kräftige Störung der Gleichgewichtsverteilung, da fortgesetzt lichtelektrisch ausgelöste Elektronen aus einem niederen in einen höheren Energiezustand gehoben werden.
Im folgenden wird ein statistischer Ansatz für die Verteilung von Elektronen über dargebotene Energiestufen versucht für den Fall, daß laufend je Sekunde eine bestimmte Anzahl aus einem tieferen in ein höheres Niveau gehoben wird.
An alternative formulation is presented of the formal theory of multi-channel scattering in nonrelativistic quantum mechanics. We start by defining spaces of state vectors, where two particles either stay together or separate in the limit t →+∞ (or — ∞), when the state vector develops in time by e–i H t (H is the complete Hamiltonian of the n-particle system). A channel is defined as a space of state vectors with the following property: Developing in time by e-i H t they asymptotically describe a state of the n-particle system, where the particles are grouped in fragments. Defining a Hamiltonian Hγ for each channel, in which—compared to H—the interactions acting between particles from different fragments are missing, it is physically plausible that lim eiH e—iHt Ψ exists for vectors Ψ in the channel. Having discussed the limit vectors (asymptotic states), the S-matrix formalism can be introduced as usual. Finally the introduction of the exclusion principle is discussed.
Es wird eine massenspektrometrische Analysenmethode für Germanium angegeben, die den quantitativen Nachweis einiger Elemente in Germanium bis zu Relativkonzentrationen von 10-5—10-6 gestattet. Diese Methode wurde auf die Messung der Verteilungskoeffizienten von B und In in Ge angewandt. Die Analysen wurden an dem mit Hilfe der Zonenschmelze1 angereicherten Ende eines Regulus durchgeführt.
Die massenspektrometrischen Analysen des Germaniumdampfes zeigten einen molekularen Ge-Anteil in der Dampfphase. Es wurden Cluster-Ionen bis zu Ge8 nachgewiesen. Auch bei Zinn und Silicium fand sich ein Cluster-Anteil in der Dampfphase.
Nach einer kurzen Zusammenstellung von Verfahren, die die Herstellung von Thermoelementen mit geringer Wärmekapazität und -ableitung ermöglichen, werden Konstruktion und thermische Daten der vom Verfasser entwickelten mikroskopisch feinen „Thermonadeln“ wiedergegeben. Um die meßtechnischen Möglichkeiten dieser Thermonadeln beurteilen zu können, wird zunächst eine einfache Theorie des Thermoelementes als Wärmekraftmaschine entwickelt: Der Nutzeffekt wird definiert als der Quotient aus der durch Peltier- und Thomson-Effekt erzeugten elektrischen Energie und den durch die an der Meßstelle des Thermoelementes reversibel und irreversibel aufgenommenen Wärmemengen. Mit Hilfe eines „Arbeitsfaktors A“ (der ein Maß für die Qualität des Thermopaares ist) wird ein theoretischer und praktischer „Gütefaktor G bzw. G“ als das Verhältnis des Nutzeffektes eines Thermoelementes zum Nutzeffekt einer Carnot-Maschine definiert. Dieses Verhältnis gibt an, um welchen Faktor der Nutzeffekt eines Thermoelementes „theoretisch“ und „praktisch“ hinter dem thermodynamisch größtmöglichen Nutzeffekt zurückbleibt. Aus der Tatsache, daß G niemals größer als 1 werden kann, wird eine obere Grenze für die Arbeitsfaktoren A ≦ 1 und damit (in Abhängigkeit.
Die Vorstellungen des Wilsonschen Halbleitermodells werden quantitativ durchgeführt und die Abhängigkeit der Fermischen Grenzenergie von Temperatur, Konzentration und Art der Störstellen berechnet. Es ergibt sich, daß die Grenzenergie das elektrische Verhalten des Halbleiters entscheidet. Bisher ungeklärte experimentelle Ergebnisse werden gedeutet.
Nach neueren Messungen besitzt das Auge eine definierte Empfindlichkeit noch bis etwa 1.0 μ. Es wird hier eine Formel mitgeteilt, die die Messungsresultate befriedigend darstellt. Ihre Auslegung deutet darauf hin, daß der Abfall der Augenempfindlichkeit in diesem "ultraroten" Bereich gerade hinreichend rasch erfolgt, daß keine Dunkelreaktion im Auge den Sehakt stört.
Eine Erweiterung des Differenzen-Verfahrens zur Berechnung von kugelsymmetrischen Temperaturfeldern
(1947)
Mit dem Differenzenverfahren können in einfacher Weise beliebige Anheiz- und Abkühlungsvorgänge, soweit sie kugelsymmetrisch verlaufen, behandelt werden. Sowohl der Fall, daß eine Kugel von einem Medium konstanter Außentemperatur umgeben wird, wie auch der Fall, daß die Temperatur ohne Störung durch Konvektion in der Umgebung der geheizten Kugel sich einstellt, wird erörtert und führt auf leicht durchführbare Rechnungen und Konstruktionen. Zum Schluß wird gezeigt, wie sich aus den angegebenen Rekursionsformeln die analytischen Gesetzmäßigkeiten der stationären Temperaturverteilung leicht elementar ableiten lassen.
Based on an e+e− collision data sample corresponding to an integrated luminosity of 2.93 fb−1 collected with the BESIII detector at √s=3.773 GeV, the first amplitude analysis of the singly Cabibbo-suppressed decay D+→K+K0Sπ0 is performed. From the amplitude analysis, the K∗(892)+K0S component is found to be dominant with a fraction of (57.1±2.6±4.2)%, where the first uncertainty is statistical and the second systematic. In combination with the absolute branching fraction B(D+→K+K0Sπ0) measured by BESIII, we obtain B(D+→K∗(892)+K0S)=(8.69±0.40±0.64±0.51)×10−3, where the third uncertainty is due to the branching fraction B(D+→K+K0Sπ0). The precision of this result is significantly improved compared to the previous measurement. This result also differs from most of theoretical predictions by about 4σ, which may help to improve the understanding of the dynamics behind.
In Memoriam: Kurt Kimpel †
(1950)
An Hand neuerer paläoklimatologischer Forschungsergebnisse wird nachgewiesen, daß sowohl die Polwanderungstheorie als auch die astronomische Theorie von Milankovitch in bezug auf die Verhältnisse während des Känozoikums und namentlich während des Alluviums versagen. Es wird weiterhin ausgeführt, daß die Nebelveränderlichkeit nicht etwa durch rein optische Bedeckungseffekte, sondern durch die Bildung einer dichten, den Stern umgebenden Hülle, welche den Energietransport in der Sternatmosphäre stört, hervorgerufen wird. Die kleineren Schwankungen innerhalb der Eiszeiten (Interstadialzeiten) und die kurzdauernden Schwankungen des Alluvialklimas können durch die faserige (Filament-) Struktur der Dunkelwolken erklärt werden.
Im ersten Teil werden kurz die entscheidenden Schwierigkeiten der beiden bekanntesten Versuche zur Erklärung der Eiszeiten, und zwar der Pol-bzw. Kontinentalver-schiebungen (Epeirophorese) und der sog. astronomischen Theorie (Schwankungen der Schiefe der Ekliptik und der Erdbahnelemente) aufgezeigt. - Im zweiten Teil wird wahrscheinlich gemacht, daß eine schon 1921 vorgetragene Hypothese von Shapley, nach der die Sonne in der diluvialen Eiszeit eine von kosmischen Dunkelwolken verursachte schwache Veränderlichkeit ihrer Strahlung zeigte, nach neueren, in erster Linie astrophysikalischen Forschungsergebnissen eine brauchbare Erklärung zu liefern imstande ist, aus folgenden drei Gründen:
1. In allen dichteren kosmischen Dunkelwolken findet man unregelmäßige veränderliche Sterne eines ganz besonderen Typus; im Gegensatz zu fast allen übrigen Typen veränderlicher Sterne handelt es sich bei diesen Sternen um Zwergsterne, wie die Sonne oder noch schwächer.
2. Unser Sonnensystem befindet sich gegenwärtig innerhalb dunkler kosmischer Materie, und es ist höchstwahrscheinlich, daß es in naher Vergangenheit auch dichtere Teile von solchen Dunkelwolken durchquert hat.
3. Die Form der Dunkelwolken, ihre armförmigen, zirrus-oder zirrostratusähnlichen Anordnungen und Verästelungen lassen eine zwanglose Erklärung der mehrfachen Wiederholung der Eiszeiten zu; es wird hier also nicht nur die Eiszeit, sondern aus der gleichen Hauptursache auch deren Gliederung erklärt, was sonst nicht gelungen zu sein scheint.
Die Mitwirkung anderer, in erster Linie astronomischer und geographischer Faktoren, letztere insbesondere in der älteren Erdgeschichte, ist durchaus möglich.
During collisions of heavy ions with heavy targets below the Coulomb barrier, adiabatic molecular orbitals are formed for the inner electrons. Deviations from adiabaticity lead to coupling between various states and can be treated by time-dependent perturbation theory. For high charges ( Z1+Z2 ≧ 60) the molecular electrons are highly relativistic. Therefore, the Dirac equation has to be used to obtain the energies and wave functions. The Dirac Hamiltonian is transformed into the intrinsic rotating coordinate system where prolate spheroidal coordinates are introduced. A set of basis functions is proposed which allows the evaluation of all matrix elements of the Dirac Hamiltonian analytically. The resulting matrix is diagonalized numerically. The finite nuclear charge distribution is also taken into account. Results are presented and discussed for various characteristic systems, e. g. Br-Br, Ni-Ni, I-I, Br-Zr, I-Au, U -U, etc.
We present a unified formulation of the interaction of electrons with the electromagnetic field in heavy ion collisions, based on quantized interacting fields. This reduces the effort in treating many-electron systems substantially, as compared with the usual S-matrix theory. Both formalisms are shown to be equivalent. The simplification achieved by our new approach is demonstrated in detail for the example of quasi-molecular radiation.
A model for the quantum yield of the coloration caused by UV-light in spiropyran layers is described. This model allows to calculate the sensitivity of layers having different compositions. The mechanism concerning the stability of the coloration is essentially clarified. Calculations of the stability for layers of different compositions are possible by a model describing the mechanism approximately.
A scattering theory for reactions with three-particle channels above the two-particle threshold is developed. The S-matrix-technique is used for the calculation of the extended S-matrix. Correlated two-particle wave functions in the exit channels are employed to describe the exact two-particle continuum. For the usual shell model only a few partial waves dominate. The cross section depends on the energy-distribution between the two outgoing nucleons. Numerical results are presented for the model (d, 2n)-reaction exciting 0+ -states in O16 without Coulomb-effects. The treatment is restricted to three (2p2h)-states with the particles in the (sd)-shell and holes in the p-shell.
Two equations for the macroscopic part W of the statistical operator are considered:
1. the master equation W = — MW, t
2. the exact equation W = — J K(t — r) W (r) dr.
It follows from the physical equivalence of the solutions together with a stability assumption and the assumption that there is a time τ* after which also the derivatives of the solutions are equivalent, that τ* is the life-time of the kernel K and that Conversely, the equivalence of the solutions follows from assumptions on the life-time of the kernel K together with a stability assumption and a smoothness assumption on the initial statistical operator W(0).
Coupled channel calculations for Coulomb and nuclear excitation of the systems 136Xe-238U and 238U-238U have been performed using the rotation-vibration model. The impact parameter-, energy-and spin-dependence of the excitation probabilities are discussed for the ground state-, β-and γ-band up to Jπ = 36+. It is shown that the energy levels and quadrupole matrix elements are strongly influenced by the rotation-vibration interaction. Analytic expressions for the elastic and coupling potentials are presented.
Introducing correlated continuum wave functions for the two- and re-particle-continuum a microscopic theory of nuclear reactions based on a method of Fano is developed. The S-matrix-elements are given by the matrix-elements between correlated continuum wave functions and bound state wave functions. The antisymmetrization of the continuum wave functions with more than one particle in the continuum is included. The theory can be straightforwardly applied on the n-nucleon-emission process following photo- and particle excitations.
The master operators B which cause the entropy production dH/dt = - k-1 dS/dt to become extremal for fixed statistical operators W are constructed and discussed. There are boundaries of the set B of master operators, B = {B | Σ B2vu = b} for which the problem is solvable yielding minimal entropy production, while no solution exists in the set B without any constraints. Operators with maximal entropy production must be extremal points of B.
The spike protein (S) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the primary focus for vaccine development. In this study, we combined cryo–electron tomography, subtomogram averaging, and molecular dynamics simulations to structurally analyze S in situ. Compared with the recombinant S, the viral S was more heavily glycosylated and occurred mostly in the closed prefusion conformation. We show that the stalk domain of S contains three hinges, giving the head unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and potentially to the development of safe vaccines.
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. We combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S is more heavily glycosylated and occurs predominantly in a closed pre-fusion conformation. We show that the stalk domain of S contains three hinges that give the globular domain unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines. The large scale tomography data set of SARS-CoV-2 used for this study is therefore sufficient to resolve structural features to below 5 Ångstrom, and is publicly available at EMPIAR-10453.
Transport of lipids across membranes is fundamental for diverse biological pathways in cells. Multiple ion-coupled transporters take part in lipid translocation, but their mechanisms remain largely unknown. Major facilitator superfamily (MFS) lipid transporters play central roles in cell wall synthesis, brain development and function, lipids recycling, and cell signaling. Recent structures of MFS lipid transporters revealed overlapping architectural features pointing towards a common mechanism. Here we used cysteine disulfide trapping, molecular dynamics simulations, mutagenesis analysis, and transport assays in vitro and in vivo, to investigate the mechanism of LtaA, a proton-dependent MFS lipid transporter essential for lipoteichoic acid synthesis in the pathogen Staphylococcus aureus. We reveal that LtaA displays asymmetric lateral openings with distinct functional relevance and that cycling through outward- and inward-facing conformations is essential for transport activity. We demonstrate that while the entire amphipathic central cavity of LtaA contributes to lipid binding, its hydrophilic pocket dictates substrate specificity. We propose that LtaA catalyzes lipid translocation by a ‘trap-and-flip’ mechanism that might be shared among MFS lipid transporters.
A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important intermediate at the branch point of these pathways and is continuously monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. In this study, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for selective binding of PA over phosphatidylserine (PS). The insertion of the AH into the membrane core renders Opi1 sensitive to the lipid acyl chain composition and provides a means to adjust membrane biogenesis. By rational design of the AH, we tune the membrane-binding properties of Opi1 and control its responsiveness in vivo. Using extensive molecular dynamics simulations, we identify two PA-selective three-finger grips that tightly bind the PA phosphate headgroup while interacting less intimately with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.
A key event in cellular physiology is the decision between membrane biogenesis and fat storage. Phosphatidic acid (PA) is an important lipid intermediate and signaling lipid at the branch point of these pathways and constantly monitored by the transcriptional repressor Opi1 to orchestrate lipid metabolism. Here, we report on the mechanism of membrane recognition by Opi1 and identify an amphipathic helix (AH) for the selective binding to membranes containing PA over phosphatidylserine (PS). The insertion of the AH into the hydrophobic core of the membrane renders Opi1 sensitive to the lipid acyl chain composition as an important factor contributing to the regulation of membrane biogenesis. Based on these findings, we rationally designed the membrane binding properties of Opi1 to control its responsiveness in the physiological context. Using extensive molecular dynamics (MD) simulations, we identified two PA-selective three-finger grips that tightly bind the phosphate headgroup, while interacting less intimately and more transiently with PS. This work establishes lipid headgroup selectivity as a new feature in the family of AH-containing membrane property sensors.
The SLC26 family of transporters maintains anion equilibria in all kingdoms of life. The family shares a 7 + 7 transmembrane segments inverted repeat architecture with the SLC4 and SLC23 families, but holds a regulatory STAS domain in addition. While the only experimental SLC26 structure is monomeric, SLC26 proteins form structural and functional dimers in the lipid membrane. Here we resolve the structure of an SLC26 dimer embedded in a lipid membrane and characterize its functional relevance by combining PELDOR/DEER distance measurements and biochemical studies with MD simulations and spin-label ensemble refinement. Our structural model reveals a unique interface different from the SLC4 and SLC23 families. The functionally relevant STAS domain is no prerequisite for dimerization. Characterization of heterodimers indicates that protomers in the dimer functionally interact. The combined structural and functional data define the framework for a mechanistic understanding of functional cooperativity in SLC26 dimers.
The SLC26 family of transporters maintains anion equilibria in all kingdoms of life. The family shares a 7 + 7 transmembrane segments inverted repeat architecture with the SLC4 and SLC23 families, but holds a regulatory STAS domain in addition. While the only experimental SLC26 structure is monomeric, SLC26 proteins form structural and functional dimers in the lipid membrane. Here we resolve the structure of an SLC26 dimer embedded in a lipid membrane and characterize its functional relevance by combining PELDOR distance measurements and biochemical studies with MD simulations and spin-label ensemble refinement. Our structural model reveals a unique interface different from the SLC4 and SLC23 families. The functionally relevant STAS domain exerts a stabilizing effect on regions central in this dimer. Characterization of heterodimers indicates that protomers in the dimer functionally interact. The combined structural and functional data define the framework for a mechanistic understanding of functional cooperativity in SLC26 dimers.
Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments
(2023)
The release of inorganic phosphate (Pi) from actin filaments constitutes a key step in their regulated turnover, which is fundamental to many cellular functions. However, the molecular mechanisms underlying Pi release from both the core and barbed end of actin filaments remain unclear. Here, we combine cryo-EM with molecular dynamics simulations and in vitro reconstitution to demonstrate how actin releases Pi through a ‘molecular backdoor’. While constantly open at the barbed end, the backdoor is predominantly closed in filament-core subunits and only opens transiently through concerted backbone movements and rotameric rearrangements of residues close to the nucleotide binding pocket. This mechanism explains why Pi escapes rapidly from the filament end and yet slowly from internal actin subunits. In an actin variant associated with nemaline myopathy, the backdoor is predominantly open in filament-core subunits, resulting in greatly accelerated Pi release after polymerization and filaments with drastically shortened ADP-Pi caps. This demonstrates that the Pi release rate from F-actin is controlled by steric hindrance through the backdoor rather than by the disruption of the ionic bond between Pi and Mg2+ at the nucleotide-binding site. Our results provide the molecular basis for Pi release from actin and exemplify how a single, disease-linked point mutation distorts the nucleotide state distribution and atomic structure of the actin filament.
Maximum likelihood estimates of diffusion coefficients from single-particle tracking experiments
(2021)
Single-molecule localization microscopy allows practitioners to locate and track labeled molecules in biological systems. When extracting diffusion coefficients from the resulting trajectories, it is common practice to perform a linear fit on mean-squared-displacement curves. However, this strategy is suboptimal and prone to errors. Recently, it was shown that the increments between the observed positions provide a good estimate for the diffusion coefficient, and their statistics are well-suited for likelihood-based analysis methods. Here, we revisit the problem of extracting diffusion coefficients from single-particle tracking experiments subject to static noise and dynamic motion blur using the principle of maximum likelihood. Taking advantage of an efficient real-space formulation, we extend the model to mixtures of subpopulations differing in their diffusion coefficients, which we estimate with the help of the expectation–maximization algorithm. This formulation naturally leads to a probabilistic assignment of trajectories to subpopulations. We employ the theory to analyze experimental tracking data that cannot be explained with a single diffusion coefficient. We test how well a dataset conforms to the assumptions of a diffusion model and determine the optimal number of subpopulations with the help of a quality factor of known analytical distribution. To facilitate use by practitioners, we provide a fast open-source implementation of the theory for the efficient analysis of multiple trajectories in arbitrary dimensions simultaneously.
The interaction between the Heat Shock Proteins 70 and 40 is at the core of the ATPase regulation of the chaperone machinery that maintains protein homeostasis. However, the structural details of the interaction remain elusive and contrasting models have been proposed for the transient Hsp70/Hsp40 complexes. Here we combine molecular simulations based on both coarse-grained and atomistic models with coevolutionary sequence analysis to shed light on this problem by focusing on the bacterial DnaK/DnaJ system. The integration of these complementary approaches resulted in a novel structural model that rationalizes previous experimental observations. We identify an evolutionarily conserved interaction surface formed by helix II of the DnaJ J-domain and a structurally contiguous region of DnaK, involving lobe IIA of the nucleotide binding domain, the inter-domain linker, and the β-basket of the substrate binding domain.
The interaction between the Heat Shock Proteins 70 and 40 is at the core of the ATPase regulation of the chaperone machinery that maintains protein homeostasis. However, the structural details of this fundamental interaction are still elusive and contrasting models have been proposed for the transient Hsp70/Hsp40 complexes. Here we combine molecular simulations based on both coarsegrained and atomistic models with co-evolutionary sequence analysis to shed light on this problem by focusing on the bacterial DnaK/DnaJ system. The integration of these complementary approaches resulted into a novel structural model that rationalizes previous experimental observations. We identify an evolutionary-conserved interaction surface formed by helix II of the DnaJ J-domain and a groove on lobe IIA of the DnaK nucleotide binding domain, involving the inter-domain linker.
TriMem: A parallelized hybrid Monte Carlo software for efficient simulations of lipid membranes
(2022)
Lipid membranes are integral building blocks of living cells and perform a multitude of biological functions. Currently, molecular simulations of cellular-scale membrane remodeling processes at atomic resolution are extremely difficult, due to their size, complexity, and the large times-scales on which these processes occur. Instead, elastic membrane models are used to simulate membrane shapes and transitions between them and to infer their properties and functions. Unfortunately, an efficiently parallelized open-source simulation code to do so has been lacking. Here, we present TriMem, a parallel hybrid Monte Carlo simulation engine for triangulated lipid membranes. The kernels are efficiently coded in C++ and wrapped with Python for ease-of-use. The parallel implementation of the energy and gradient calculations and of Monte Carlo flip moves of edges in the triangulated membrane enable us to simulate large and highly curved membrane structures. For validation, we reproduce phase diagrams of vesicles with varying surface-to-volume ratios and area difference. We also compute the density of states to verify correct Boltzmann sampling. The software can be used to tackle a range of large-scale membrane remodeling processes as a step toward cell-scale simulations. Additionally, extensive documentation make the software accessible to the broad biophysics and computational cell biology communities.
Abstract
The primary immunological target of COVID-19 vaccines is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface and mediates viral entry into the host cell. To identify possible antibody binding sites, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation, and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for structure-based vaccine design. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics. The protective glycan shield and the high flexibility of its hinges give the stalk overall low epitope scores. Our computational epitope-mapping procedure is general and should thus prove useful for other viral envelope proteins whose structures have been characterized.
Author summary
The SARS-CoV-2 virus has caused a global health crisis. The spike protein exposed at its surface is key for infection and the primary antibody target. However, spike is covered by highly mobile glycan molecules that could impair antibody binding. To identify accessible epitopes, we performed molecular dynamics simulations of an atomistic model of glycosylated spike embedded in a membrane. By combining extensive simulations with bioinformatics analyses, we recovered known antibody binding sites and identified several epitope candidates as targets for further vaccine development.