Molecular dynamics simulations of proteins: can the explicit water model be varied?

In molecular mechanics simulations of biological systems, the solvation water is typically represented by a default water model which is an integral part of the force field. Indeed, protein nonbonding parameters are chosen in order to obtain a balance between water-water and protein-water interactions and hence a reliable description of protein solvation. However, less attention has been paid to the question of whether the water model provides a reliable description of the water properties under the chosen simulation conditions, for which more accurate water models often exist. Here we consider the case of the CHARMM protein force field, which was parametrized for use with a modified TIP3P model. Using quantum mechanical and molecular mechanical calculations, we investigate whether the CHARMM force field can be used with other water models: TIP4P and TIP5P. Solvation properties of N-methylacetamide (NMA), other small solute molecules, and a small protein are examined. The results indicate differences in binding energies and minimum energy geometries, especially for TIP5P, but the overall description of solvation is found to be similar for all models tested. The results provide an indication that molecular mechanics simulations with the CHARMM force field can be performed with water models other than TIP3P, thus enabling an improved description of the solvent water properties.

Ferric and ferrous iron in nitroso-myoglobin: computer simulations of stable and metastable states and their infrared spectra

The binding of NO to iron is involved in the biological function of many heme proteins. Contrary to ligands like CO and O-2, which only bind to ferrous (Fe-II) iron, NO binds to both ferrous and ferric (Fe-II) iron. In a particular protein, the natural oxidation state can therefore be expected to be tailored to the required function. Herein, we present an ob initio potential-energy surface for ferric iron interacting with NO. This potential-energy surface exhibits three minima corresponding to eta'-NO coordination (the global minimum), eta(1)-ON coordination and eta(2) coordination. This contrasts with the potential-energy surface for Fe-II-NO, which ex- hibits only two minima (the eta(2) coordination mode for Fe-II is a transition state, not a minimum). In addition, the binding energies of NO are substantially larger for Fe-III than for Fe-II. We have performed molecular dynamics simulations for NO bound to ferric myoglobin (Mb(III)) and compare these with results obtained for Mb(II). Over the duration of our simulations (1.5 ns), all three binding modes are found to be stable at 200 K and transiently stable at 300 K, with eventual transformation to the eta(1)-NO global-minimum conformation. We discuss the implication of these results related to studies of rebinding processes in myoglobin.

Computer simulations of structures, energetics and dynamics of myoglobin center dot center dot center dot ligand complexes

Myoglobin has been studied in considerable detail using different experimental and computational techniques over the past decades. Recent developments in time-resolved spectroscopy have provided experimental data amenable to detailed atomistic simulations. The main theme of the present review are results on the structures, energetics and dynamics of ligands ( CO, NO) interacting with myoglobin from computer simulations. Modern computational methods including free energy simulations, mixed quantum mechanics/molecular mechanics simulations, and reactive molecular dynamics simulations provide insight into the dynamics of ligand dynamics in confined spaces complementary to experiment. Application of these methods to calculate and understand experimental observations for myoglobin interacting with CO and NO are presented and discussed.

CO migration in native and mutant myoglobin: atomistic simulations for the understanding of protein function

Molecular dynamics simulations of the events after the photodissociation of CO in the myoglobin mutant L29F in which leucine is replaced by phenylalanine are reported. Using both classical and mixed quantum-classical molecular dynamics calculations, we observed the rapid motion of CO away from the distal heme pocket to other regions of the protein, in agreement with recent experimental results. The experimentally observed and calculated infrared spectra of CO after dissociation are also in good agreement. We compared the results with data from simulations of WT myoglobin. As the time resolution of experimental techniques is increased, theoretical methods and models can be validated at the atomic scale by direct comparison with experiment.

Coupled chemistry climate model simulations of stratospheric temperatures and their trends for the recent past

Temperature results from multi-decadal simulations of coupled chemistry climate models for the recent past are analyzed using multi-linear regression including a trend, solar cycle, lower stratospheric tropical wind, and volcanic aerosol terms. The climatology of the models for recent years is in good agreement with observations for the troposphere but the model results diverge from each other and from observations in the stratosphere. Overall, the models agree better with observations than in previous assessments, primarily because of corrections in the observed temperatures. The annually averaged global and polar temperature trends simulated by the models are generally in agreement with revised satellite observations and radiosonde data over much of their altitude range. In the global average, the model trends underpredict the radiosonde data slightly at the top of the observed range. Over the Antarctic some models underpredict the temperature trend in the lower stratosphere, while others overpredict the trends

Efficient on the fly calculation of time correlation functions in computer simulations

Time correlation functions yield profound information about the dynamics of a physical system and hence are frequently calculated in computer simulations. For systems whose dynamics span a wide range of time, currently used methods require significant computer time and memory. In this paper, we discuss the multiple-tau correlator method for the efficient calculation of accurate time correlation functions on the fly during computer simulations. The multiple-tau correlator is efficacious in terms of computational requirements and can be tuned to the desired level of accuracy. Further, we derive estimates for the error arising from the use of the multiple-tau correlator and extend it for use in the calculation of mean-square particle displacements and dynamic structure factors. The method described here, in hardware implementation, is routinely used in light scattering experiments but has not yet found widespread use in computer simulations.

On differentiating ground clutter and insect echoes from Doppler weather radars using archived data

Normally wind measurements from Doppler radars rely on the presence of rain. During fine weather, insects become a potential radar target for wind measurement. However, it is difficult to separate ground clutter and insect echoes when spectral or polarimetric methods are not available. Archived reflectivity and velocity data from repeated scans provide alternative methods. The probability of detection (POD) method, which maps areas with a persistent signal as ground clutter, is ineffective when most scans also contain persistent insect echoes. We developed a clutter detection method which maps the standard deviation of velocity (SDV) over a large number of scans, and can differentiate insects and ground clutter close to the radar. Beyond the range of persistent insect echoes, the POD method more thoroughly removes ground clutter. A new, pseudo-probability clutter map was created by combining the POD and SDV maps. The new map optimised ground clutter detection without removing insect echoes.

Effect of headgroup size, charge, and solvent structure on polymer−micelle interactions, studied by molecular dynamics simulations

We performed atomistic molecular dynamics simulations of anionic and cationic micelles in the presence of poly(ethylene oxide) (PEO) to understand why nonionic water-soluble polymers such as PEO interact strongly with anionic micelles but only weakly with cationic micelles. Our micelles include sodium n-dodecyl sulfate (SDS), n-dodecyl trimethylammonium chloride (DTAC), n-dodecyl ammonium chloride (DAC), and micelles in which we artificially reverse the sign of partial charges in SDS and DTAC. We observe that the polymer interacts hydrophobically with anionic SDS but only weakly with cationic DTAC and DAC, in agreement with experiment. However, the polymer also interacts with the artificial anionic DTAC but fails to interact hydrophobically with the artificial cationic SDS, illustrating that large headgroup size does not explain the weak polymer interaction with cationic micelles. In addition, we observe through simulation that this preference for interaction with anionic micelles still exists in a dipolar "dumbbell" solvent, indicating that water structure and hydrogen bonding alone cannot explain this preferential interaction. Our simulations suggest that direct electrostatic interactions between the micelle and polymer explain the preference for interaction with anionic micelles, even though the polymer overall carries no net charge. This is possible given the asymmetric distribution of negative charges on smaller atoms and positive charges oil larger units in the polymer chain.

Molecular dynamics simulations of threadlike cetyltrimethylammonium chloride micelles: effects of sodium chloride and sodium salicylate salts

We use atomistic molecular dynamics simulations to probe the effects of added sodium chloride (NaCl) and sodium salicylate (NaSal) salts on the spherical-to-threadlike micelle shape transition in aqueous solutions of cetyltrimethylammonium chloride (CTAC) surfactants. Long threadlike micelles are found to be unstable and break into spherical micelles at low concentrations or NaCl, but remain stable for 20 ns above a threshold value of [NaCl] approximate to 3.0 M, which is about 2.5 times larger than the experimental salt concentration at which the transition between spherical and rodlike micelles occurs. The chloride counterions associate weakly oil the surface of the CTAC micelles with the degree of counterion dissociation decreasing slightly with increasing [NaCl] on spherical micelles, but dropping significantly on the threadlike micelles tit high [NaCl]. This effect indicates that the electrolyte ions drive the micellar shape transition by screening the electrostatic repulsions between the micellar headgroups, The aromatic salicylate counterions, on the other hand, penetrate inside the micelle with their hydrophilic groups staying in the surfactant headgroup region and the hydrophobic groups partially embedded into the hydrophobic core of the micelle. The strong association of the salicylate ions with the surfactant headgroups leads to dense packing of the surfactant molecules, which effectively reduces the surface area per surfactant, and increases intramicellar ordering of the surfactant headgroups, favoring the formation of long threadlike micelles. Simulation predictions of the geometric and electrostatic properties of the spherical and threadlike micelles are in good agreement with experiments.

A comparison of stratosphere-troposphere transport in convection-permitting and convection-parameterizing simulations of three mesoscale convective systems

The transport of stratospheric air into the troposphere within deep convection was investigated using the Met Office Unified Model version 6.1. Three cases were simulated in which convective systems formed over the UK in the summer of 2005. For each of these three cases, simulations were performed on a grid having 4 km horizontal grid spacing in which the convection was parameterized and on a grid having 1 km horizontal grid spacing, which permitted explicit representation of the largest energy-containing scales of deep convection. Cross-tropopause transport was diagnosed using passive tracers that were initialized above the dynamically defined tropopause (2 potential vorticity unit surface) with a mixing ratio of 1. Although the synoptic-scale environment and triggering mechanisms varied between the cases, the total simulated transport was similar in all three cases. The total stratosphere-to-troposphere transport over the lifetime of the convective systems ranged from 25 to 100 kg/m2 across the simulated convective systems and resolutions, which corresponds to ∼5–20% of the total mass located within a stratospheric column extending 2 km above the tropopause. In all simulations, the transport into the lower troposphere (defined as below 3.5 km elevation) accounted for ∼1% of the total transport across the tropopause. In the 4 km runs most of the transport was due to parameterized convection, whereas in the 1 km runs the transport was due to explicitly resolved convection. The largest difference between the simulations with different resolutions occurred in the one case of midlevel convection considered, in which the total transport in the 1 km grid spacing simulation with explicit convection was 4 times that in the 4 km grid spacing simulation with parameterized convection. Although the total cross-tropopause transport was similar, stratospheric tracer was deposited more deeply to near-surface elevations in the convection-parameterizing simulations than in convection-permitting simulations.

Some physical drivers of changes in the winter storm tracks over the North Atlantic and Mediterranean during the Holocene

The winter climate of Europe and the Mediterranean is dominated by the weather systems of the mid-latitude storm tracks. The behaviour of the storm tracks is highly variable, particularly in the eastern North Atlantic, and has a profound impact on the hydroclimate of the Mediterranean region. A deeper understanding of the storm tracks and the factors that drive them is therefore crucial for interpreting past changes in Mediterranean climate and the civilizations it has supported over the last 12 000 years (broadly the Holocene period). This paper presents a discussion of how changes in climate forcing (e.g. orbital variations, greenhouse gases, ice sheet cover) may have impacted on the ‘basic ingredients’ controlling the mid-latitude storm tracks over the North Atlantic and the Mediterranean on intermillennial time scales. Idealized simulations using the HadAM3 atmospheric general circulation model (GCM) are used to explore the basic processes, while a series of timeslice simulations from a similar atmospheric GCM coupled to a thermodynamic slab ocean (HadSM3) are examined to identify the impact these drivers have on the storm track during the Holocene. The results suggest that the North Atlantic storm track has moved northward and strengthened with time since the Early to Mid-Holocene. In contrast, the Mediterranean storm track may have weakened over the same period. It is, however, emphasized that much remains still to be understood about the evolution of the North Atlantic and Mediterranean storm tracks during the Holocene period.

A comparison of space weather analysis techniques used to predict the arrival of the Earth-directed CME and its shockwave launched on 8 April 2010

The Earth-directed coronal mass ejection (CME) of 8 April 2010 provided an opportunity for space weather predictions from both established and developmental techniques to be made from near–real time data received from the SOHO and STEREO spacecraft; the STEREO spacecraft provide a unique view of Earth-directed events from outside the Sun-Earth line. Although the near–real time data transmitted by the STEREO Space Weather Beacon are significantly poorer in quality than the subsequently downlinked science data, the use of these data has the advantage that near–real time analysis is possible, allowing actual forecasts to be made. The fact that such forecasts cannot be biased by any prior knowledge of the actual arrival time at Earth provides an opportunity for an unbiased comparison between several established and developmental forecasting techniques. We conclude that for forecasts based on the STEREO coronagraph data, it is important to take account of the subsequent acceleration/deceleration of each CME through interaction with the solar wind, while predictions based on measurements of CMEs made by the STEREO Heliospheric Imagers would benefit from higher temporal and spatial resolution. Space weather forecasting tools must work with near–real time data; such data, when provided by science missions, is usually highly compressed and/or reduced in temporal/spatial resolution and may also have significant gaps in coverage, making such forecasts more challenging.

Cloud-resolving simulations of deep convection over a heated mountain

Cloud-resolving numerical simulations of airflow over a diurnally heated mountain ridge are conducted to explore the mechanisms and sensitivities of convective initiation under high pressure conditions. The simulations are based on a well-observed convection event from the Convective and Orographically Induced Precipitation Study (COPS) during summer 2007, where an isolated afternoon thunderstorm developed over the Black Forest mountains of central Europe, but they are idealized to facilitate understanding and reduce computational expense. In the conditionally unstable but strongly inhibited flow under consideration, sharp horizontal convergence over the mountain acts to locally weaken the inhibition and moisten the dry midtroposphere through shallow cumulus detrainment. The onset of deep convection occurs not through the deep ascent of a single updraft but rather through a rapid succession of thermals that are vented through the mountain convergence zone into the deepening cloud mass. Emerging thermals rise through the saturated wakes of their predecessors, which diminishes the suppressive effects of entrainment and allows for rapid glaciation above the freezing level as supercooled cloud drops rime onto preexisting ice particles. These effects strongly enhance the midlevel cloud buoyancy and enable rapid ascent to the tropopause. The existence and vigor of the convection is highly sensitive to small changes in background wind speed U0, which controls the strength of the mountain convergence and the ability of midlevel moisture to accumulate above the mountain. Whereas vigorous deep convection develops for U0 = 0 m s−1, deep convection is completely eliminated for U0 = 3 m s−1. Although deep convection is able to develop under intermediate winds (U0 = 1.5 m s−1), its formation is highly sensitive to small-amplitude perturbations in the initial flow.