Structural Transformations of Ice at High Pressures Via Molecular Dynamics Simulations

Abstract

A simple classical model is used for the study of the structural transformations of ice under high pressures, such as ice VIII to VII and X, via classical molecular dynamics (MD) simulation. In the present MD simulation, pair potentials of a simple form between pair of atoms and a thee-body potential representing the H-O-H angle dependence, originally developed by Kawamura et al., were used. Starting with a stable ice VIII at low pressure and low temperature, we have carried out two different MD runs, one with increasing pressure keeping the temperature constant (simulation I) and the other with increasing temperature under constant pressure (simulation II). From these MD simulations we have obtained the structural transformations from ice VIII to VII for both simulations; the former was finally transformed into ice X for the simulation I. The present results are compatible with recent experiments on high pressure ices.     

Comparative study of stability and transport of molecules through cyclic peptide nanotube and aquaporin: a molecular dynamics simulation approach

Abstract

The structural stability and transport properties of the cyclic peptide nanotube (CPN) 8?×?[Cys–Gly–Met–Gly]₂ in different phospholipid bilayers such as POPA (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidic acid), POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine), POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol) and POPS (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine) with water have been investigated using molecular dynamics (MD) simulation. The hydrogen bonds and non-bonded interaction energies were calculated to study the stability in different bilayers. One µs MD simulation in POPA lipid membrane reveals the stability of the cyclic peptide nanotube, and the simulations at various temperatures manifest the higher stability of 8?×?[Cys–Gly–Met–Gly]₂. We demonstrated that the presence of sulphur-containing amino acids in CPN enhances the stability through disulphide bonds between the adjacent rings. Further, the water permeation coefficient of the CPN is calculated and compared with human aquaporin-2 (AQP2) channel protein. It is found that the coefficients are highly comparable to the AQP2 channel though the mechanism of water transport is not similar to AQP 2; the flow of water in the CPN is taking place as a two-line 1–2–1–2 file fashion. In addition to that, the transport behavior of Na⁺ and K⁺ ions, single water molecule, urea and anti-cancer drug fluorouracil were investigated using pulling simulation and potential of mean force calculation. The above transport behavior shows that Na⁺ is trapped in CPN for a longer time than other molecules. Also, the interactions of the ions and molecules in Cα and mid-Cα plane were studied to understand the transport behavior of the CPN. Abbreviations AQP2 Aquaporin-2

CPN Cyclic peptide nanotube

MD Molecular dynamics

POPA 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphatidic acid

POPE 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine

POPG 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol

POPS 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine

Communicated by Ramaswamy H. Sarma     

Molecular Dynamics Study of BaB2O4 in Crystalline and Molten States

Abstract

Structural aspects of BaB₂O₄ liquids have been investigated by the molecular dynamics simulation including the determination on the parameters of the interatomic potential applicable to BaB₂O₄ in both crystalline and molten states. The structure and physical properties of BaB₂O₄ crystals were successfully reproduced by the MD simulation for both α and β phases. The simulated interference function in the liquid state was also in good agreement with the experimental one. Several interesting features on the relaxation phenomena just after melting were reproduced by the simulation that the structure factors of simulated liquid maintain the characteristic features of the original crystal structure for more than 40ps after melting, and the variation of the number of rings formed by B-O bondings was found to increase after melting.     

Hydration of Nucleic Acid Bases Studied Using Novel Atom-Atom Potential Functions

Abstract

New simple atom-atom potential functions for simulating behavior of nucleic acids and their fragments in aqueous solutions are suggested. These functions contain terms which are inversely proportional to the first (electrostatics), sixth (or tenth for the atoms, forming hydrogen bonds) and twelfth (repulsion of all the atoms) powers of interatomic distance. For the refinement of the potential function parameters calculations of ice lattice energy, potential energy and configuration of small clusters consisting of water and nucleic acid base molecules as well as Monte Carlo simulation of liquid water were performed. Calculations using new potential functions give rise to more linear hydrogen bonds between water and base molecules than using other potentials. Sites of preferential hydration of five nucleic bases—uracil, thymine, cytosine, guanine and adenine as well as of 6,6,9-trimethyladenine were found. In the most energetically favourable sites water molecule interacts with two adjacent hydrophilic centres of the base. Studies of interaction of the bases with several water molecules showed that water-water interaction play an important role in the arrangement of the nearest to the base water molecules. Hydrophilic centres are connected by “bridges” formed by hydrogen bonded water molecules. The results obtained are consistent with crystallographic and mass-spectrometric data.     

Trifonov's Meta-Definition of Life

Abstract

We present here results on 260 pico seconds (ps) molecular dynamics (MD) simulation of substance P (SP) in hydrated bilayer of dimyristoyl phosphatidyl choline (DMPC) (39 molecules of DMPC with 776 water molecules). 260 ps MD simulation has been carried out in 0.001 ps time interval with united atom force field, using AMBER 4.0 package. Non bonded pair list was updated every 20 cycles using 12.5 Å cut off distance. Analysis of MD data is done using our package ANALMD. The obtained models are presented using graphics package RASMOL. All simulations, analysis of MD data and graphics is done on INDIGO-2, R-4400 extreme graphics work station. Our results show no systematic change in order parameter, but reduction in transfraction of the chain torsional angles, compared to our earlier results on MD simulation on hydrated DMPC bilayer without SP. C-terminal and central peptide residues adopt partial helical conformation. Helix type as classified on the basis of H-bonds is between a and 3₁₀. The peptide backbone shows flexibility during heating runs. Later, it is stabilized and there was not much change in the spatial position of the backbone. Lipid matrix serves the role of immobilization of the peptide backbone in a preferred conformation.     

Cryosphere: ice on Niwot Ridge and in the Green Lakes Valley,Colorado Front Range

Background: Subsurface ice preserved as ice lenses and within rock glaciers as well as glacial and lake ice provides sensitive indicators of climate change and serve as a late-season source of meltwater.

Aims: We synthesise the results of geomorphological, geophysical and geochemical studies during the period of 1995–2014, building on a long history of earlier work focused on ice and permafrost studies on Niwot Ridge and the adjacent Green Lakes Valley (GLV), which is part of the Niwot Ridge Long Term Ecological Research Site.

Methods: These studies are discussed in the context of how bodies of ice and rock glaciers reflect changing local climate. We review recent results from geophysical investigations (resistivity, seismic refraction and ground-penetrating radar) of the shallow subsurface, ongoing monitoring of the Arikaree Glacier, three rock glaciers and lake ice in the GLV, and interpretations of how subsurface ice melt regulates the flow and chemistry of alpine surface water after seasonal snowfields melt.

Results and conclusions: Permafrost conditions reported from Niwot Ridge in the 1970s are generally absent today, but ice lenses form and melt seasonally. Ice is present permanently within the Green Lakes 5 rock glacier and at nearby favourable sites. The Arikaree Glacier has shown a marked decline in cumulative mass balance during the past 12 years after a 30-year period when net mass balance was ca. 0. Duration of seasonal lake ice increases with elevation in GLV, but duration has decreased at all seven lakes that have been monitored during the last three decades. This decrease has been most marked at the lowest elevation where it amounted to a reduction of about 1 d year^?1 and least at Green Lake 5 where the loss has been at a rate of 0.5 d year^?1. Surface temperature measurements from rock glaciers have not shown strong trends during the past 15 years. It has been suggested that almost all of the 2.5-mm year^?1 increase in stream discharge from the upper GLV in September and October has been derived from melting of subsurface ice.     

Ab Initio Molecular Dynamics for Simple Liquid Metals Based on the Hypernetted-Chain Approximation

Abstract

We present an ab initio molecular dynamics (MD) method for simple liquid metals based on the quantal hypernetted-chain (QHNC) theory derived from exact expressions for radial distribution functions (RDF's) of the electron-ion model for liquid metals. In our method based on the QHNC equations, the classical MD is performed repeatedly to determine a self-consistent effective interionic potential, which depends on the ion-ion RDF of the system. This resultant effective ionic potential is obtained to be consistent with the density distribution of a pseudoatom and the electron-ion RDF, as well as the ion-ion RDF and the ion-ion bridge function, which are determined exactly as a result of the repeated MD simulation. We have applied this QHNC-MD method for Li, Na, K, Rb, and Cs near the melting temperature using upto 16,000 particles for the MD simulation. It is found that the convergence of the effective interionic potential is fast enough for practical applications; typically two MD runs are enough for convergence of the effective ionic potential within accuracy of 3 to 4 digits. Furthermore the resultant static structure factor is in excellent agreement with experimental data of X-ray and/or neutron scatering.     

On the Uniqueness of the Reverse Monte Carlo Simulation for Molecular Liquids

Abstract

A careful analysis of the three dimensional structures of liquid Chlorine produced by the Reverse Monte Carlo (RMC) and Molecular Dynamics (MD) techniques is presented. The analysis allows us to measure the degree of uniqueness between the potential and the atom-atom distribution functions, g _aa(r), in the case of pairwise potentials formed by isotropic and anisotropic site-site interactions. The g _aa(r) obtained from MD simulations are used as ‘experimental’ input data in the RMC procedure and the constraint of rigid molecules is imposed. The particle configurations produced by RMC are then studied by using a recently proposed general method for analysing the local order in liquids. The same analysis applied to the particle configurations produced by the conventional MD simulation yields a set of partial distribution functions which relates the main features of the g _aa(r) to microscopic pair geometries. The comparison between the partial centre-centre g _cc(r) shows that the three dimensional structures, produced by MD and RMC simulations, agree very well when only isotropic site-site interactions act. In this case RMC produces the same radial distribution function g(r, ω₁, ω₂) as that obtained from the original MD configurations; it is therefore a valid tool for deriving a complete information on the physical properties of a fluid. For anisotropic site-site interactions the partial g _cc(r) of MD and RMC differ significantly and show that the three dimensional structures, produced by MD and RMC simulations, differ too. The discrepancies are particularly evident for the T shaped configurations and affect the values of the potential energy. Therefore, even if the potential is purely pairwise additive, the use of the atomic radial distribution function as input data and the imposition of atomic constraints which model the molecules as hard dumbbells are not sufficient to bring the RMC procedure towards the ‘true’ microscopic structure of the liquid; the presence of non central forces between sites disrupts the bijective correspondence between the potential and the g _aa(r).     

A Molecular Dynamics Computer Simulation Study of Nucleotide Analogues. Comparison of the Hydration Pattern of Dithymidine Phosphate with those of the Dithymidine Methylphosphonate Diastereomers

Abstract

The hydration pattern of thymidyl(3′→5′) thymidine 1 and those of R_p and S_p diastereomers of the corresponding methylphosphonate analogue 2, have been studied using Molecular Dynamics (MD) computer simulation. It was found that the methylphosphonate modification leads to significant changes in the coordination of water molecules around the internucleotidic linkage and these, in turn, affect the hydration pattern of other parts of the molecule. The most notable differences between R_p and S_p diastereomers 2a and 2b were found to occur at the deoxyribose moieties of the nucleosid-5′-yl units.     

A Molecular Dynamics Simulation of an Aqueous Beryllium Chloride Solution

Abstract

A Molecular Dynamics simulation of a 1.1 molal aqueous BeCl₂ solution was performed with the flexible BJH model for water and a newly developed three-body potential for Be²⁺ -H₂O interactions derived from ab-initio calculations. The properties of the potential are discussed and radial distribution functions, angular distributions and dynamic properties of the solution like vibrational modes and hindered rotations are analyzed.     

Structure of the Sm Binding Site From Human U4 snRNA Derived From a 3 ns PME Molecular Dynamics Simulation

Abstract

A molecular dynamics simulation of the Sm binding site from human U4 snRNA was undertaken to determine the conformational flexibility of this region and to identify RNA conformations that were important for binding of the Sm proteins. The RNA was fully-solvated (>9,000 water molecules) and charge neutralized by inclusion of potassium ions. A three nanosecond MD simulation was conducted using AMBER with long-range electrostatic forces considered using the particle mesh Ewald summation method. The initial model of the Sm binding site region had the central and 3′ stem-loops that flanked the Sm site co-axial with one another, and with the single-stranded Sm binding site region ([I] conformation). During the course of the trajectory, the axes of the 3′ stem-loop, and later the central stem-loop, became roughly orthogonal from their original anti-parallel orientation. As these conformational changes occurred, the snRNA adopted first an [L] conformation, and finally a [U] conformation. The [U] conformation was more stable than either the [I] or [L] conformations, and persisted for the final 1 ns of the trajectory. Analysis of the structure resulting from the MD simulations revealed the bulged nucleotide, U₁₁₄, and the mismatched A₉₁-G₁₁₀ base pair provided distinctive structural features that may enhance Sm protein binding. Based on the results of the MD simulation and the available experimental data, we proposed a mechanism for the binding of the Sm protein sub-complexes to the snRNA. In this model, the D₁/D₂ and E/F/G Sm protein sub-complexes first bind the snRNA in the [U] conformation, followed by conformational re-arrangement to the [I] conformation and binding of the D₃/B Sm protein sub-complex.     

New heat shock protein (Hsp90) inhibitors,designed by pharmacophore modeling and virtual screening: synthesis,biological evaluation and molecular dynamics studies

Abstract

Inhibition of heat shock protein 90 (Hsp90) is known to be a significantly effective strategy in cancer therapy. Here, pyrazolopyranopyrimidine derivatives were characterized as new Hsp90 inhibitors. The molecules’ key structure (ZINC02819805) was determined by utilizing a pharmacophore model virtual screening workflow. Structural optimization was then carried out on compound ZINC02819805, pyrazolopyranopyrimidine derivatives were designed and six chosen derivatives were synthesized. The inhibition of Hsp90 ATPase activity of synthesized compounds revealed that para methylphenyl derivative of pyrazolopyranopyrimidine (HM3) was the most potent inhibitor (IC₅₀ = 5.5?µM). The anti-proliferative activity of this compound was evaluated against a panel of cell lines including MCF-7, HeLa and HUVEC (IC₅₀ = 1.28?µM, IC₅₀ = 1.74?µM and IC₅₀ = 61.48?µM respectively) by MTT method. The western blot analysis of treated MCF-7 cells with compound HM3 showed that the expression level of Hsp70 and Her2 proteins changed. The high level of Hsp70 expression and low level of Her2 expression suggest that compound HM3 exhibits inhibitory effect on Hsp90. Finally, the key interactions between HM3 and Hsp90 protein were studied by molecular dynamics simulation and showed that compound HM3 was stable in Hsp90 active cite during 200?ns simulation. Abbreviations Hsp90 Heat shock protein 90

MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

ATP adenosine triphosphate

MD molecular dynamics simulation

RMSD root-mean-square deviation

RMSF root-mean-square fluctuation

Rg gyration radius

m-SABNPs boehmite nanoparticles-supported sulfamic acid

Communicated by Ramaswamy H. Sarma     

Abundance and composition of the sea-ice meiofauna in off-shore pack ice of the Beaufort Gyre in summer 2002 and 2003

We studied the abundance, biomass and potential ingestion rates of meiofauna in multi-year sea ice (MYI) of the Beaufort Gyre during two icebreaker expeditions in summers 2002 and 2003. Ice cores were taken at a total of ten stations and analyzed for ice temperature, salinity, chlorophyll a (Chl a), and ice meiofauna abundances. In 2002, ice was free of snow and covered with melt ponds. In 2003, snow still covered the ice and a slush-layer was found in the ice-water interface. The vertical distribution of Chl a mostly followed C-shaped curves with elevated concentrations at the bottom and top of the ice. Ice meiofauna was mainly restricted to the bottom 10 cm of the ice and was dominated by turbellarians, harpacticoid copepods and nematodes. The meiofauna abundances (range: 8–3,000 individuals m^–2) and Chl a concentration (range: 0.1–1.7 mg Chl a m^–2) were similar to estimates for MYI of the Transpolar Drift, but about 2 orders of magnitude below coastal fast first-year ice estimates. Calculated potential meiofaunal ingestion rate, based on allometric equations and volume estimates from the literature, was about 1% of published daily algal production rates and was thus unlikely to constrain algal biomass accumulation.     

Molecular Dynamics Study of Li2SiO3 in the Liquid and Glassy States

Abstract

Molecular dynamics simulation (MD) has been carried out for Li₂SiO₃ in the molten and glassy states. The parameters of the pair potential functions were determined by a trial and error method so that the results of X-ray diffraction analysis could be well reproduced.

The changes in the structure and dynamic properties accompanied by lowering temperature revealed that the glass transition of this simulated system occurred between 973 and 700 K. The ratio of the bridging oxygens to non-bridging oxygens was nearly constant over the investigated temperature range, while a small change in the pattern of branching of the -Si-O-framework was found. The second peaks in the pair correlation functions g_Si-O(r) and g_Si-Si(r) split at lower temperature. These splittings suggest that the motion changing the relative orientations of two neighboring SiO₄ units may be nearly frozen at lower temperature.     

Life cycle assessment of California unsweetened almond milk

Purpose

Plant-based alternatives to dairy milk have grown in popularity over the last decade. Almond milk comprises the largest share of plant-based milk in the US market and, as with so many food products, stakeholders in the supply chain are increasingly interested in understanding the environmental impacts of its production, particularly its carbon footprint and water consumption. This study undertakes a life cycle assessment (LCA) of a California unsweetened almond milk.

Methods

The scope of this LCA includes the production of almond milk in primary packaging at the factory gate. California produces all US almonds, which are grown under irrigated conditions. Spatially resolved modeling of almond cultivation and primary data collection from one almond milk supply chain were used to develop the LCA model. While the environmental indicators of greatest interest are global warming potential (GWP) and freshwater consumption (FWC), additional impact categories from US EPA’s TRACI assessment method are also calculated. Co-products are accounted for using economic allocation, but mass-based allocation and displacement are also tested to understand the effect of co-product allocation choices on results.

Results and discussion

The GWP and FWC of one 48 oz. (1.42 L) bottle of unsweetened almond milk are 0.71 kg CO₂e and 175 kg of water. A total of 0.39 kg CO₂e (or 55%) of the GWP is attributable to the almond milk, with the remainder attributable to packaging. Almond cultivation alone is responsible for 95% of the FWC (167 kg H₂O), because of irrigation water demand. Total primary energy consumption (TPE) is estimated at 14.8 MJ. The 48 oz. (1.42 L) PET bottle containing the almond milk is the single largest contributor to TPE (42%) and GWP (35%). Using recycled PET instead of virgin PET for the bottle considerably reduces all impact indicators except for eutrophication potential.

Conclusions

For the supply chain studied here, packaging choices provide the most immediate opportunities for reducing impacts related to GWP and TPE, but would not result in a significant reduction in FWC because irrigation water for almond cultivation is the dominant consumer. To provide context for interpretation, average US dairy milk appears to have about 4.5 times the GWP and 1.8 times the FWC of the studied almond milk on a volumetric basis.

     

A coarse-grain MD (molecular dynamic) simulation of PCL–PEG and PLA–PEG aggregation as a computational model for prediction of the drug-loading efficacy of doxorubicin

Abstract

Formulating a hydrophobic drug that is water-soluble is a pharmaceutical challenge. One way is to incorporate the drug in an amphiphilic micelle composed from an aggregation of block copolymers. Design of a good nano-micelle requires many trial-and-error attempts. In this article, we developed a computational model based on a coarse-grained molecular dynamic (MD) simulation and correlated outputs with previous studies. A good correlation shows that this model reliably simulates poly-lactic acid–poly-ethylene glycol (PLA–PEG) and poly-caprolactone (PCL)–PEG aggregation in water with and without the presence of doxorubicin.

Communicated by Ramaswamy H. Sarma     

A Transferable Interatomic Potential for Calcium Carbonate

Abstract

The development of an interatomic potential for calcium carbonate is described. The potential is fitted to calcite and then transferred to aragonite. The calculated structure and trend in lattice energies are both compared with experimental values.     

Inhibitor binding studies of Mycobacterium tuberculosis MraY (Rv2156c): Insights from molecular modeling,docking, and simulation studies

Abstract

Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis (M.tb) or tubercule bacillus, and H37Rv is the most studied clinical strain. The recent development of resistance to existing drugs is a global health-care challenge to control and cure TB. Hence, there is a critical need to discover new drug targets in M.tb. The members of peptidoglycan biosynthesis pathway are attractive target proteins for antibacterial drug development. We have performed in silico analysis of M.tb MraY (Rv2156c) integral membrane protein and constructed the three-dimensional (3D) structure model of M.tb MraY based on homology modeling method. The validated model was complexed with antibiotic muraymycin D2 (MD2) and was used to generate structure-based pharmacophore model (e-pharmacophore). High-throughput virtual screening (HTVS) of Asinex database and molecular docking of hits was performed to identify the potential inhibitors based on their mode of interactions with the key residues involved in M.tb MraY–MD2 binding. The validation of these molecules was performed using molecular dynamics (MD) simulations for two best identified hit molecules complexed with M.tb MraY in the lipid bilayer, dipalmitoylphosphatidyl-choline (DPPC) membrane. The results indicated the stability of the complexes formed and retained non-bonding interactions similar to MD2. These findings may help in the design of new inhibitors to M.tb MraY involved in peptidoglycan biosynthesis.