Computational chemistry for elucidating protein function: energetics and dynamics of myoglobin-ligand systems

State-of-the-art computational methodologies are used to investigate the energetics and dynamics of photodissociated CO and NO in myoglobin (Mb···CO and Mb···NO). This includes the combination of molecular dynamics, ab initio MD, free energy sampling, and effective dynamics methods to compare the results with studies using X-ray crystallography and ultrafast spectroscopy metho ds. It is shown that modern simulation techniques along with careful description of the intermolecular interactions can give quantitative agreement with experiments on complex molecular systems. Based on this agreement predictions for as yet uncharacterized species can be made.

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.

Constraint release in entangled binary blends of linear polymers: a molecular dynamics study

We present extensive molecular dynamics simulations of the dynamics of diluted long probe chains entangled with a matrix of shorter chains. The chain lengths of both components are above the entanglement strand length, and the ratio of their lengths is varied over a wide range to cover the crossover from the chain reptation regime to tube Rouse motion regime of the long probe chains. Reducing the matrix chain length results in a faster decay of the dynamic structure factor of the probe chains, in good agreement with recent neutron spin echo experiments. The diffusion of the long chains, measured by the mean square displacements of the monomers and the centers of mass of the chains, demonstrates a systematic speed-up relative to the pure reptation behavior expected for monodisperse melts of sufficiently long polymers. On the other hand, the diffusion of the matrix chains is only weakly perturbed by the diluted long probe chains. The simulation results are qualitatively consistent with the theoretical predictions based on constraint release Rouse model, but a detailed comparison reveals the existence of a broad distribution of the disentanglement rates, which is partly confirmed by an analysis of the packing and diffusion of the matrix chains in the tube region of the probe chains. A coarse-grained simulation model based on the tube Rouse motion model with incorporation of the probability distribution of the tube segment jump rates is developed and shows results qualitatively consistent with the fine scale molecular dynamics simulations. However, we observe a breakdown in the tube Rouse model when the short chain length is decreased to around N-S = 80, which is roughly 3.5 times the entanglement spacing N-e(P) = 23. The location of this transition may be sensitive to the chain bending potential used in our simulations.

Integration of chaos theory and mathematical models in building simulation: Part I: Literature review

Current mathematical models in building research have been limited in most studies to linear dynamics systems. A literature review of past studies investigating chaos theory approaches in building simulation models suggests that as a basis chaos model is valid and can handle the increasingly complexity of building systems that have dynamic interactions among all the distributed and hierarchical systems on the one hand, and the environment and occupants on the other. The review also identifies the paucity of literature and the need for a suitable methodology of linking chaos theory to mathematical models in building design and management studies. This study is broadly divided into two parts and presented in two companion papers. Part (I) reviews the current state of the chaos theory models as a starting point for establishing theories that can be effectively applied to building simulation models. Part (II) develops conceptual frameworks that approach current model methodologies from the theoretical perspective provided by chaos theory, with a focus on the key concepts and their potential to help to better understand the nonlinear dynamic nature of built environment systems. Case studies are also presented which demonstrate the potential usefulness of chaos theory driven models in a wide variety of leading areas of building research. This study distills the fundamental properties and the most relevant characteristics of chaos theory essential to building simulation scientists, initiates a dialogue and builds bridges between scientists and engineers, and stimulates future research about a wide range of issues on building environmental systems.

Integration of chaos theory and mathematical models in building simulation: Part II: Conceptual frameworks

Current mathematical models in building research have been limited in most studies to linear dynamics systems. A literature review of past studies investigating chaos theory approaches in building simulation models suggests that as a basis chaos model is valid and can handle the increasing complexity of building systems that have dynamic interactions among all the distributed and hierarchical systems on the one hand, and the environment and occupants on the other. The review also identifies the paucity of literature and the need for a suitable methodology of linking chaos theory to mathematical models in building design and management studies. This study is broadly divided into two parts and presented in two companion papers. Part (I), published in the previous issue, reviews the current state of the chaos theory models as a starting point for establishing theories that can be effectively applied to building simulation models. Part (II) develop conceptual frameworks that approach current model methodologies from the theoretical perspective provided by chaos theory, with a focus on the key concepts and their potential to help to better understand the nonlinear dynamic nature of built environment systems. Case studies are also presented which demonstrate the potential usefulness of chaos theory driven models in a wide variety of leading areas of building research. This study distills the fundamental properties and the most relevant characteristics of chaos theory essential to (1) building simulation scientists and designers (2) initiating a dialogue between scientists and engineers, and (3) stimulating future research on a wide range of issues involved in designing and managing building environmental systems.

How predation and landscape fragmentation affect vole population dynamics

Background: Microtine species in Fennoscandia display a distinct north-south gradient from regular cycles to stable populations. The gradient has often been attributed to changes in the interactions between microtines and their predators. Although the spatial structure of the environment is known to influence predator-prey dynamics of a wide range of species, it has scarcely been considered in relation to the Fennoscandian gradient. Furthermore, the length of microtine breeding season also displays a north-south gradient. However, little consideration has been given to its role in shaping or generating population cycles. Because these factors covary along the gradient it is difficult to distinguish their effects experimentally in the field. The distinction is here attempted using realistic agent-based modelling. Methodology/Principal Findings: By using a spatially explicit computer simulation model based on behavioural and ecological data from the field vole (Microtus agrestis), we generated a number of repeated time series of vole densities whose mean population size and amplitude were measured. Subsequently, these time series were subjected to statistical autoregressive modelling, to investigate the effects on vole population dynamics of making predators more specialised, of altering the breeding season, and increasing the level of habitat fragmentation. We found that fragmentation as well as the presence of specialist predators are necessary for the occurrence of population cycles. Habitat fragmentation and predator assembly jointly determined cycle length and amplitude. Length of vole breeding season had little impact on the oscillations. Significance: There is good agreement between our results and the experimental work from Fennoscandia, but our results allow distinction of causation that is hard to unravel in field experiments. We hope our results will help understand the reasons for cycle gradients observed in other areas. Our results clearly demonstrate the importance of landscape fragmentation for population cycling and we recommend that the degree of fragmentation be more fully considered in future analyses of vole dynamics.

Parameterisation of orographic cloud dynamics in a GCM

A new parameterisation is described that predicts the temperature perturbations due to sub-grid scale orographic gravity waves in the atmosphere of the 19 level HadAM3 version of the United Kingdom Met Office Unified Model. The explicit calculation of the wave phase allows the sign of the temperature perturbation to be predicted. The scheme is used to create orographic clouds, including cirrus, that were previously absent in model simulations. A novel approach to the validation of this parameterisation makes use of both satellite observations of a case study, and a simulation in which the Unified Model is nudged towards ERA-40 assimilated winds, temperatures and humidities. It is demonstrated that this approach offers a feasible way of introducing large scale orographic cirrus clouds into GCMs.

Segmental dynamics in entangled linear polymer melts

We present molecular dynamics (MD) and slip-springs model simulations of the chain segmental dynamics in entangled linear polymer melts. The time-dependent behavior of the segmental orientation autocorrelation functions and mean-square segmental displacements are analyzed for both flexible and semiflexible chains, with particular attention paid to the scaling relations among these dynamic quantities. Effective combination of the two simulation methods at different coarse-graining levels allows us to explore the chain dynamics for chain lengths ranging from Z ≈ 2 to 90 entanglements. For a given chain length of Z ≈ 15, the time scales accessed span for more than 10 decades, covering all of the interesting relaxation regimes. The obtained time dependence of the monomer mean square displacements, g1(t), is in good agreement with the tube theory predictions. Results on the first- and second-order segmental orientation autocorrelation functions, C1(t) and C2(t), demonstrate a clear power law relationship of C2(t) C1(t)m with m = 3, 2, and 1 in the initial, free Rouse, and entangled (constrained Rouse) regimes, respectively. The return-to-origin hypothesis, which leads to inverse proportionality between the segmental orientation autocorrelation functions and g1(t) in the entangled regime, is convincingly verified by the simulation result of C1(t) g1(t)−1 t–1/4 in the constrained Rouse regime, where for well-entangled chains both C1(t) and g1(t) are rather insensitive to the constraint release effects. However, the second-order correlation function, C2(t), shows much stronger sensitivity to the constraint release effects and experiences a protracted crossover from the free Rouse to entangled regime. This crossover region extends for at least one decade in time longer than that of C1(t). The predicted time scaling behavior of C2(t) t–1/4 is observed in slip-springs simulations only at chain length of 90 entanglements, whereas shorter chains show higher scaling exponents. The reported simulation work can be applied to understand the observations of the NMR experiments.

Simulation models in farming systems research : potential and challenges

Integrated simulation models can be useful tools in farming system research. This chapter reviews three commonly used approaches, i.e. linear programming, system dynamics and agent-based models. Applications of each approach are presented and strengths and drawbacks discussed. We argue that, despite some challenges, mainly related to the integration of different approaches, model validation and the representation of human agents, integrated simulation models contribute important insights to the analysis of farming systems. They help unravelling the complex and dynamic interactions and feedbacks among bio-physical, socio-economic, and institutional components across scales and levels in farming systems. In addition, they can provide a platform for integrative research, and can support transdisciplinary research by functioning as learning platforms in participatory processes.

The Aqua-Planet Experiment (APE): CONTROL SST Simulation

Climate simulations by 16 atmospheric general circulation models (AGCMs) are compared on an aqua-planet, a water-covered Earth with prescribed sea surface temperature varying only in latitude. The idealised configuration is designed to expose differences in the circulation simulated by different models. Basic features of the aqua-planet climate are characterised by comparison with Earth. The models display a wide range of behaviour. The balanced component of the tropospheric mean flow, and mid-latitude eddy covariances subject to budget constraints, vary relatively little among the models. In contrast, differences in damping in the dynamical core strongly influence transient eddy amplitudes. Historical uncertainty in modelled lower stratospheric temperatures persists in APE. Aspects of the circulation generated more directly by interactions between the resolved fluid dynamics and parameterized moist processes vary greatly. The tropical Hadley circulation forms either a single or double inter-tropical convergence zone (ITCZ) at the equator, with large variations in mean precipitation. The equatorial wave spectrum shows a wide range of precipitation intensity and propagation characteristics. Kelvin mode-like eastward propagation with remarkably constant phase speed dominates in most models. Westward propagation, less dispersive than the equatorial Rossby modes, dominates in a few models or occurs within an eastward propagating envelope in others. The mean structure of the ITCZ is related to precipitation variability, consistent with previous studies. The aqua-planet global energy balance is unknown but the models produce a surprisingly large range of top of atmosphere global net flux, dominated by differences in shortwave reflection by clouds. A number of newly developed models, not optimised for Earth climate, contribute to this. Possible reasons for differences in the optimised models are discussed. The aqua-planet configuration is intended as one component of an experimental hierarchy used to evaluate AGCMs. This comparison does suggest that the range of model behaviour could be better understood and reduced in conjunction with Earth climate simulations. Controlled experimentation is required to explore individual model behaviour and investigate convergence of the aqua-planet climate with increasing resolution.

Simulation of a domestic ground source heat pump system using a three-dimensional numerical borehole heat exchanger model

Common approaches to the simulation of borehole heat exchangers (BHEs) assume heat transfer in circulating fluid and grout to be in a quasi-steady state and ignore fluctuations in fluid temperature due to transport of the fluid around the loop. However, in domestic ground source heat pump (GSHP) systems, the heat pump and circulating pumps switch on and off during a given hour; therefore, the effect of the thermal mass of the circulating fluid and the dynamics of fluid transport through the loop has important implications for system design. This may also be important in commercial systems that are used intermittently. This article presents transient simulation of a domestic GSHP system with a single BHE using a dynamic three-dimensional (3D) numerical BHE model. The results show that delayed response associated with the transit of fluid along the pipe loop is of some significance in moderating swings in temperature during heat pump operation. In addition, when 3D effects are considered, a lower heat transfer rate is predicted during steady operations. These effects could be important when considering heat exchanger design and system control. The results will be used to develop refined two-dimensional models.

The emergence and use of diagramming in system dynamics: a critical account

The paper reviews the leading diagramming methods employed in system dynamics to communicate the contents of models. The main ideas and historical development of the field are first outlined. Two diagramming methods—causal loop diagrams (CLDs) and stock/flow diagrams (SFDs)—are then described and their advantages and limitations discussed. A set of broad research directions is then outlined. These concern: the abilities of different diagrams to communicate different ideas, the role that diagrams have in group model building, and the question of whether diagrams can be an adequate substitute for simulation modelling. The paper closes by suggesting that although diagrams alone are insufficient, they have many benefits. However, since these benefits have emerged only as ‘craft wisdom’, a more rigorous programme of research into the diagrams' respective attributes is called for.

System dynamics mapping of acute patient flows

Department of Health staff wished to use systems modelling to discuss acute patient flows with groups of NHS staff. The aim was to assess the usefulness of system dynamics (SD) in a healthcare context and to elicit proposals concerning ways of improving patient experience. Since time restrictions excluded simulation modelling, a hybrid approach using stock/flow symbols from SD was created. Initial interviews and hospital site visits generated a series of stock/flow maps. A ‘Conceptual Framework’ was then created to introduce the mapping symbols and to generate a series of questions about different patient paths and what might speed or slow patient flows. These materials formed the centre of three workshops for NHS staff. The participants were able to propose ideas for improving patient flows and the elicited data was subsequently employed to create a finalized suite of maps of a general acute hospital. The maps and ideas were communicated back to the Department of Health and subsequently assisted the work of the Modernization Agency.