Effect of the thermostat in the molecular dynamics simulation on the folding of the model protein chignolin

Molecular dynamics simulations of the model protein chignolin with explicit solvent were carried out, in order to analyze the influence of the Berendsen thermostat on the evolution and folding of the peptide. The dependence of the peptide behavior on temperature was tested with the commonly employed thermostat scheme consisting of one thermostat for the protein and another for the solvent. The thermostat coupling time of the protein was increased to infinity, when the protein is not in direct contact with the thermal bath, a situation known as minimally invasive thermostat. In agreement with other works, it was observed that only in the last situation the instantaneous temperature of the model protein obeys a canonical distribution. As for the folding studies, it was shown that, in the applications of the commonly utilized thermostat schemes, the systems are trapped in local minima regions from which it has difficulty escaping. With the minimally invasive thermostat the time that the protein needs to fold was reduced by two to three times. These results show that the obstacles to the evolution of the extended peptide to the folded structure can be overcome when the temperature of the peptide is not directly controlled.     

Modeling of the three-dimensional structure of polypeptides in solution using potential-scaled/hot-solute molecular dynamics.

We present here an efficient and accurate procedure for modeling of the three-dimensional structures of polypeptides in the explicit solvent water based on molecular dynamics calculations. Using the toxic domain analog of heat-stable enterotoxin as a model peptide, we examined the utilities of two molecular dynamics techniques with the system containing the explicit solvent. One is the potential-scaled molecular dynamics that had been designed for effective conformational analyses of biomolecules with the explicit solvent water by partially scaling down the potential energies involved in the solute molecules. The other is the variation of Berendsen's weak coupling method (referred to as "hot-solute" method), in which only the solute of the system is heated to a high temperature while the solvent is kept at a normal temperature. Each method successfully increased the rate of folding of the peptides, and the most effective was a combination of the two methods. Moreover, the final structure obtained via cooling process successfully reproduced the experimentally known structure from the extended amino acid sequence using only the distance restraints representing three disulfide bonds in the peptide. Additional distance restraints derived from some of the NOE cross peaks accelerated the folding of the peptide, but gave almost the same structure as in the case without these additional restraints. Because a similar calculation without the explicit solvent could not reproduce the known structure, it is suggested that the explicit solvent water could play an important role in the modeling. The methods presented here have the potential for accurate modeling even when less experimental information was available.     

Analysis of energy and friction coefficient fluctuations of a Lennard-Jones liquid coupled to the Nosé–Hoover thermostat

Thermal fluctuations of a many-body system coupled to a Nosé–Hoover thermostat depend on the strength of the coupling parameter τ*. A wrong choice may bring non-ergodic features and non-canonical fluctuations. Here, we analyse by means of molecular dynamics simulations both the energy fluctuations and the spectrum of the friction coefficient ζ^* of an extended Lennard-Jones system in a wide range of τ* at liquid density. Three ranges of τ* are identified – small, intermediate and large, plus their transitions. For τ* values in the intermediate range, ζ^* shows chaotic behaviour, and the particle system requires reasonable computing time for its thermalisation. As a result, the extended system is ergodic and energy fluctuations are canonical and stable in time. On the contrary, small and large ranges of τ* reveal clear evidence of periodicity in the thermostat variable, for instance by propagating the initial temperature condition. For these two ranges, the extended system shows non-ergodic features and energy fluctuations are non-canonical. For large τ*, micro-canonical fluctuations are occasionally obtained. For small to intermediate and intermediate to large ranges of τ*, the thermostat variable exhibits beat waves and is thus unable to reach equilibrium no matter how extended in time the simulations are. Here, we compare our results with previous work and explain the differences.     

Molecular dynamics study of the lauryl alcohol-laurate model bilayer

Molecular dynamics (MD) calculation of the fluid phase lauryl alcohol-laurate bilayer has been executed based on Berendsen's surface-constrained model. Structure and dynamics of the bilayer have been investigated by analyzing the trajectories of the chain configurations. Newly defined correlation functions as well as the conventional ones showed that the tilt and bend of the chain play an important role in the bilayer structure, including behavior of the order parameter. Interpenetration of the layers as well as formation of collectively ordered small domains was also found. The calculated lateral diffusion coefficient was in satisfactory agreement with the experimental one. Successive jumps of the head group, rather than the hydrodynamic continuous motion, were observed. Between the jumps, the molecule librated in a local site. Time-dependent autocorrelation functions showed evidence of several different modes of the chain motion, whose time constant ranged from a few tenths of picoseconds to several tens of picoseconds.     

Ad hoc continuum-atomistic thermostat for modeling heat flow in molecular dynamics simulations

An ad hoc thermostating procedure that couples a molecular dynamics (MD) simulation and a numerical solution to the continuum heat flow equation is presented. The method allows experimental thermal transport properties to be modeled without explicitly including electronic degrees of freedom in a MD simulation. The method is demonstrated using two examples, heat flow from a constant temperature silver surface into a single crystal bulk, and a tip sliding along a silver surface. For the former it is shown that frictional forces based on the Hoover thermostat applied locally to grid regions of the simulation are needed for effective feedback between the atomistic and continuum equations. For fast tip sliding the thermostat results in less surface heating, and higher frictional and normal forces compared to the same simulation without the thermostat.     

Parametric dependence on shear viscosity of SPC/E water from equilibrium and non-equilibrium molecular dynamics simulations

A parametric dependent study is crucial for the accurate determination of transport coefficients such as shear viscosity. In this study, we calculate the shear viscosity of extended simple point charge water using a transverse current auto-correlation function (TCAF) from equilibrium molecular dynamics (EMD) and the periodic perturbation method from non-equilibrium molecular dynamics (NEMD) simulations for varying coupling time and system sizes. Results show that the shear viscosity calculated using EMD simulations with different thermostats varies significantly with coupling times and system size. The use of Berendsen and velocity-rescale thermostats in NEMD simulations generates a significant drift from the target temperature and results in an inconsistent shear viscosity with coupling time and system size. The use of Nosé–Hoover thermostat in NEMD simulations offers thermodynamic stability which results in a consistent shear viscosity for various coupling times and system sizes.     

The temperature factor and magnetic noise under the conditions of stochastic resonance of magnetosomes

The influence of magnetic noise on the dynamics of magnetic nanoparticles under the conditions of stochastic resonance is considered. The effect of the magnetic noise is shown to be equivalent to the growth of the effective thermostat temperature for the particles at the permanent actual temperature of the medium. This regularity may be used for testing the hypothesis on the involvement of magnetic nanoparticles in the formation of biological effects of weak magnetic fields.     

Temperature factor and magnetic noise under conditions of stochastic resonance of magnetosomes

The influence of magnetic noise on the dynamics of magnetic nanoparticles under stochastic resonance conditions is considered. The effect of magnetic noise on the nanoparticles at a fixed actual ambient temperature is equivalent to an increase in the effective temperature of the thermostat. This observation may be used to test whether magnetic nanoparticles are involved in the biological effects of weak magnetic fields.     

Computation of elastic constants of solids using molecular simulation: comparison of constant volume and constant pressure ensemble methods

We compute the elastic stiffness tensor of fcc argon at 60 K and 1 bar using molecular simulation tools. Three different methods are investigated: explicit deformations of the simulation box, strain fluctuations at constant pressure and stress fluctuations at constant volume. Statistical ensemble sampling is done using molecular dynamics and Monte Carlo simulations. We observe a good agreement between the different methods and sampling algorithms excepted with molecular dynamics simulations in the (NpT) ensemble. There, we notice a strong dependence of the computed elastic constants with the barostat parameter, whereas molecular dynamics simulations in the (NVT) ensemble are not affected by the thermostat parameter.     

Molecular dynamics studies in nanoscale liquid structures: geometry and thermal effects on nanojet development

Conventional macroscopic jet theory relies heavily on experimental correlations which cannot be easily extended to the nanoscale regime. Moreover, the fluid dynamic effects at small length scales and their contribution to the development of nanoscale liquid structures are fundamentally different from their macroscopic counterparts. This coupled with the high spatial and temporal resolution requirements at nanoscale domains make molecular dynamics (MD) an excellent tool for studying such structures. In this study, the formation and breakup of nanojets (NJs) developing from high pressure into vacuum is investigated using MD based on non-Hamiltonian formulations. By ejecting the equilibrated argon atoms through various nozzle geometries and diameters, nanoscale jet flows were generated. The dependence of the jet structure on nozzle geometry and diameter is studied. The influence of geometry on NJ formation is also studied along with issues involved in the equilibration and thermostat coupling parameter. Various thermostats are compared to understand the role they play in MD simulations of liquid nanostructures. Tuning of the thermostat coupling parameter has also been discussed. The jet breakup phenomenon is analysed and a comparative study, vis-à-vis, well-established continuum and stochastic models, is attempted.     

Method for the individual maintenance of mollusks infected with Schistosoma larvae in a thermostatic apparatus

A technique has been suggested for individual maintenance of intermediate hosts of Schistosoma mansoni, molluscs of the genus Biomphalaria, in thermostat water bath with thermoregulator in order to study the host-parasite relationships in the mollusc-trematode system. Advantages of the suggested technique have been shown for studying total production of Cercaria when estimating the compatibility degree of various strains of S. mansoni and races of molluscs of some species of the genus Biomphalaria.     

Consistent Temperature Coupling with Thermal Fluctuations of Smooth Particle Hydrodynamics and Molecular Dynamics

We propose a thermodynamically consistent and energy-conserving temperature coupling scheme between the atomistic and the continuum domain. The coupling scheme links the two domains using the DPDE (Dissipative Particle Dynamics at constant Energy) thermostat and is designed to handle strong temperature gradients across the atomistic/continuum domain interface. The fundamentally different definitions of temperature in the continuum and atomistic domain – internal energy and heat capacity versus particle velocity – are accounted for in a straightforward and conceptually intuitive way by the DPDE thermostat. We verify the here-proposed scheme using a fluid, which is simultaneously represented as a continuum using Smooth Particle Hydrodynamics, and as an atomistically resolved liquid using Molecular Dynamics. In the case of equilibrium contact between both domains, we show that the correct microscopic equilibrium properties of the atomistic fluid are obtained. As an example of a strong non-equilibrium situation, we consider the propagation of a steady shock-wave from the continuum domain into the atomistic domain, and show that the coupling scheme conserves both energy and shock-wave dynamics. To demonstrate the applicability of our scheme to real systems, we consider shock loading of a phospholipid bilayer immersed in water in a multi-scale simulation, an interesting topic of biological relevance.     

Transport diffusivities of fluids in nanopores by non-equilibrium molecular dynamics simulation

We present a method to study fluid transport through nanoporous materials using highly efficient non-equilibrium molecular dynamics simulations. A steady flow is induced by applying an external field to the fluid particles within a small slab of the simulation cell. The external field generates a density gradient between both sides of the porous material, which in turn triggers a convective flux through the porous medium. The heat dissipated by the fluid flow is released by a Gaussian thermostat applied to the wall particles. This method is effective for studying diffusivities in a slit pore as well as more natural, complex wall geometries. The dependence of the diffusive flux on the external field sheds light on the transport diffusivities and allows a direct calculation of effective diffusivities. Both pore and fluid particle interactions are represented by coarse-grained molecular models in order to present a proof-of-concept and to retain computational efficiency in the simulations. The application of the method is demonstrated in two different scenarios, namely the effective mass transport through a slit pore and the calculation of the effective self-diffusion through this system. The method allows for a distinction between diffusive and convective contributions of the mass transport.     

Adaptation processes in natural Drosophila populations in radiation contaminated Belarus regions before and after radiation exposure removal

We have shown that natural drosophila populations from the settlement Vetka of Gomel region with increased radiation background are more adapted to mutagenic effect of radiation than drosophila populations from Berezinsky reserve (the control). After the populations were placed into laboratory thermostat adaptation of Vetka population remained within 6-8 generations without irradiation. However the control population became more resistant too. So, the keeping of natural drosophila populations under laboratory conditions was a stress and led to unspecific adaptation the same as a low level of radiocontamination did. These facts should be considered in studying dynamics of the mutation level during radionuclide removal in animals caught in radiocontaminated regions and placed in vivaria conditions.     

Are black-box models of thermoregulatory control obsolete? The importance of borrowed knowledge.

Black-box models of thermoregulatory control have gained increasing importance in describing the properties of the biological thermostat and in devising working hypotheses for further experimental analysis. Incorporation of knowledge acquired independently from the systems analysis approach into black-box models of thermoregulation has proven useful in improving their predictive ability. The pieces of "borrowed knowledge" from independent analysis which are currently utilized in devising models of homeothermic thermoregulation comprise: the proportional control property of the biological thermostat, the Sherringtonian principles of synaptic interaction, the multiple input control of thermoregulatory effectors with differential input-effector coupling, the lack of significant thermosensory contribution from the hypothalamus in birds, the existence of warm and cold receptors and the thermal characteristics of their responses, and the Q10-type temperature dependence of temperature signal transmission within the central nervous system. Consideration of these pieces of borrowed knowledge has resulted in black-box models of temperature regulation in which explicit set-point terms are avoided.     

Molecular Dynamics Simulations of Molecules in Uniform Flow

Flow at the molecular level induces shear-induced unfolding of single proteins and can drive their assembly, the mechanisms of which are not completely understood. To be able to analyze the role of flow on molecules, we present uniform-flow molecular dynamics simulations at atomic level. The pull module of the GRoningen MAchine for Chemical Simulations package was extended to be able to force-group atoms within a defined layer of the simulation box. Application of this external enforcement to explicit water molecules, together with the coupling to a thermostat, led to a uniform terminal velocity of the solvent water molecules. We monitored the density of the whole system to establish the conditions under which the simulated flow is well-behaved. A maximal velocity of 1.3 m/s can be generated if a pull slice of 8 nm is used, and high velocities would require larger pull slices to still maintain a stable density. As expected, the target velocity increases linearly with the total external force applied. Finally, we suggest an appropriate setup to stretch a protein by uniform flow, in which protein extensions depend on the flow conditions. Our implementation provides an efficient computational tool to investigate the effect of the flow at the molecular level.     

Thermally modified azocasein--a new insoluble substrate for the determination of proteolytic activity

An insoluble chromogenic substrate for the determination of proteolytic activity was prepared by heating azocasein in a thin layer at 200 degrees C for 4 h in a hot-air thermostat. The activity of an extracellular bacterial proteinase produced by Bacillus sp. was determined with this new substrate.     

D1S80 PCR with the $25 thermal cycler

This article outlines the construction of an automatic two-step thermal cycler, using a hot water heater thermostat and light bulb, and documents its utility in performing D1S80 PCR DNA fingerprinting.     

Why does a cell monolayer replicate the metal tray pattern of the thermostat?

Cells freshly seeded into the closed culture flasks or dishes and placed on the metal tray with holes of the thermostat or incubator are seen to form the layer with uneven density: with high density corresponding to the flask bottom regions above the metal and low density corresponding to the flask bottom region above the holes in the tray. The effect was shown using several cell lines with different degrees of transformation and saturation density, including Swiss 3T3. The main cause of this effect is the difference between the temperature inside the thermostat and the lower temperature of the flasks with culture medium (rather than between the metal framework and the air), together with a high heat conduction of the metal. The reverse difference in the temperatures (higher temperature of the culture flasks) leads to the formation of the reverse pattern of the cell layer, with higher density corresponding to the holes. The temperature differences exert their influence presumably during the first 10-15 minutes after the cells seeding, when the process of cell sedimentation is involved possibly by creating the microcurrents in the medium.