Use of a novel Hill-climbing genetic algorithm in protein folding simulations

We have developed a novel Hill-climbing genetic algorithm (GA) for simulation of protein folding. The program (written in C) builds a set of Cartesian points to represent an unfolded polypeptide's backbone. The dihedral angles determining the chain's configuration are stored in an array of chromosome structures that is copied and then mutated. The fitness of the mutated chain's configuration is determined by its radius of gyration. A four-helix bundle was used to optimise simulation conditions, and the program was compared with other, larger, genetic algorithms on a variety of structures. The program ran 50% faster than other GA programs. Overall, tests on 100 non-redundant structures gave comparable results to other genetic algorithms, with the Hill-climbing program running from between 20 and 50% faster. Examples including crambin, cytochrome c, cytochrome B and hemerythrin gave good secondary structure fits with overall alpha carbon atom rms deviations of between 5 and 5.6 Angstrom with an optimised hydrophobic term in the fitness function. (C) 2003 Elsevier Ltd. All rights reserved.

Towards data warehousing and mining of protein unfolding simulation data

OBJECTIVES: The prediction of protein structure and the precise understanding of protein folding and unfolding processes remains one of the greatest challenges in structural biology and bioinformatics. Computer simulations based on molecular dynamics (MD) are at the forefront of the effort to gain a deeper understanding of these complex processes. Currently, these MD simulations are usually on the order of tens of nanoseconds, generate a large amount of conformational data and are computationally expensive. More and more groups run such simulations and generate a myriad of data, which raises new challenges in managing and analyzing these data. Because the vast range of proteins researchers want to study and simulate, the computational effort needed to generate data, the large data volumes involved, and the different types of analyses scientists need to perform, it is desirable to provide a public repository allowing researchers to pool and share protein unfolding data. METHODS: To adequately organize, manage, and analyze the data generated by unfolding simulation studies, we designed a data warehouse system that is embedded in a grid environment to facilitate the seamless sharing of available computer resources and thus enable many groups to share complex molecular dynamics simulations on a more regular basis. RESULTS: To gain insight into the conformational fluctuations and stability of the monomeric forms of the amyloidogenic protein transthyretin (TTR), molecular dynamics unfolding simulations of the monomer of human TTR have been conducted. Trajectory data and meta-data of the wild-type (WT) protein and the highly amyloidogenic variant L55P-TTR represent the test case for the data warehouse. CONCLUSIONS: Web and grid services, especially pre-defined data mining services that can run on or 'near' the data repository of the data warehouse, are likely to play a pivotal role in the analysis of molecular dynamics unfolding data.

Grid computing solutions for distributed repositories of protein folding and unfolding simulations

The P-found protein folding and unfolding simulation repository is designed to allow scientists to perform analyses across large, distributed simulation data sets. There are two storage components in P-found: a primary repository of simulation data and a data warehouse. Here we demonstrate how grid technologies can support multiple, distributed P-found installations. In particular we look at two aspects, first how grid data management technologies can be used to access the distributed data warehouses; and secondly, how the grid can be used to transfer analysis programs to the primary repositories --- this is an important and challenging aspect of P-found because the data volumes involved are too large to be centralised. The grid technologies we are developing with the P-found system will allow new large data sets of protein folding simulations to be accessed and analysed in novel ways, with significant potential for enabling new scientific discoveries.

P-found: grid-enabling distributed repositories of protein folding and unfolding simulations for data mining

The P-found protein folding and unfolding simulation repository is designed to allow scientists to perform data mining and other analyses across large, distributed simulation data sets. There are two storage components in P-found: a primary repository of simulation data that is used to populate the second component, and a data warehouse that contains important molecular properties. These properties may be used for data mining studies. Here we demonstrate how grid technologies can support multiple, distributed P-found installations. In particular, we look at two aspects: firstly, how grid data management technologies can be used to access the distributed data warehouses; and secondly, how the grid can be used to transfer analysis programs to the primary repositories — this is an important and challenging aspect of P-found, due to the large data volumes involved and the desire of scientists to maintain control of their own data. The grid technologies we are developing with the P-found system will allow new large data sets of protein folding simulations to be accessed and analysed in novel ways, with significant potential for enabling scientific discovery.

Folding of graphene slit like pore walls—a simple method of improving CO2 separation from mixtures with CH4 or N2

We report for the first time a detailed procedure for creating a simulation model of energetically stable, folded graphene-like pores and simulation results of CO2/CH4 and CO2/N2 separation using these structures. We show that folding of graphene structures is a very promising method to improve the separation of CO2 from mixtures with CH4 and N2. The separation properties of the analyzed materials are compared with carbon nanotubes having similar diameters or S/V ratio. The presented results have potential importance in the field of CO2 capture and sequestration.

Simulation of monsoon disturbances in the LMD GCM

The monsoon depressions that form over India during the summer are analyzed using simulations from the Laboratoire de Meteorologie Dynamique general circulation model. This type of synoptic system often occurs with a frequency of one to two per month and can produce a strong Indian rainfall. Two kinds of analyses are conducted in this study. The first one is a subjective analysis based on the evolution of the precipitation rate and the pattern of the sea level pressure. The second one is an objective analysis performed using the TRACK program, which identifies and tracks the minima in the sea level pressure anomaly held and computes the statistics for the distribution of systems. The analysis of a 9-yr control run, which simulates strong precipitation rates over the foothills of the Himalayas and over southern India but weak rates over central India, shows that the number of disturbances is coo low and that they almost never occur during August, when break conditions prevail. The generated disturbances more often move north, toward the foothills of the Himalayas. Another analysis is performed to study the effect of the Tibetan Plateau elevation on these disturbances with a 9-yr run carried out with a Tibetan Plateau at 50% of its current height. It is shown that this later integration simulates more frequent monsoon disturbances, which move rather northwestward, in agreement with the current observations. The comparison between the two runs shows that the June-July-August rainfall difference is in large part due to changes in the occurrence of the monsoon disturbances.

Simulation of the diurnal cycle in a climate model and its evaluation using data from Meteosat 7

The representation of the diurnal cycle in the Hadley Centre climate model is evaluated using simulations of the infrared radiances observed by Meteosat 7. In both the window and water vapour channels, the standard version of the model with 19 levels produces a good simulation of the geographical distributions of the mean radiances and of the amplitude of the diurnal cycle. Increasing the vertical resolution to 30 levels leads to further improvements in the mean fields. The timing of the maximum and minimum radiances reveals significant model errors, however, which are sensitive to the frequency with which the radiation scheme is called. In most regions, these errors are consistent with well documented errors in the timing of convective precipitation, which peaks before noon in the model, in contrast to the observed peak in the late afternoon or evening. When the radiation scheme is called every model time step (half an hour), as opposed to every three hours in the standard version, the timing of the minimum radiance is improved for convective regions over central Africa, due to the creation of upper-level layer-cloud by detrainment from the convection scheme, which persists well after the convection itself has dissipated. However, this produces a decoupling between the timing of the diurnal cycles of precipitation and window channel radiance. The possibility is raised that a similar decoupling may occur in reality and the implications of this for the retrieval of the diurnal cycle of precipitation from infrared radiances are discussed.

Numerical simulation of baroclinic waves with a parameterized boundary layer

A dry three-dimensional baroclinic life cycle model is used to investigate the role of turbulent fluxes of heat and momentum within the boundary layer on mid-latitude cyclones. Simulations are performed of life cycles for two basic states, both with and without turbulent fluxes. The different basic states produce cyclones with contrasting frontal and mesoscale-flow structures. The analysis focuses on the generation of potential-vorticity (PV) in the boundary layer and its subsequent transport into the free troposphere. The dynamic mechanism through which friction mitigates a barotropic vortex is that of Ekman pumping. This has often been assumed to be also the dominant mechanism for baroclinic developments. The PV framework highlights an additional, baroclinic mechanism. Positive PV is generated baroclinically due to friction to the north-east of a surface low and is transported out of the boundary layer by a cyclonic conveyor belt flow. The result is an anomaly of increased static stability in the lower troposphere which restricts the growth of the baroclinic wave. The reduced coupling between lower and upper levels can be sufficient to change the character of the upper-level evolution of the mature wave. The basic features of the baroclinic damping mechanism are robust for different frontal structures, with and without turbulent heat fluxes, and for the range of surface roughness found over the oceans.

Improved simulation of water vapour and clear-sky radiation using 24 hour forecasts from ERA40

Monthly mean water vapour and clear-sky radiation extracted from the European Centre for Medium Range Weather Forecasts 40-year reanalysis (ERA40) forecasts are assessed using satellite observations and additional reanalysis data. There is a marked improvement in the interannual variability of column-integrated water vapour (CWV) over the oceans when using the 24-hour forecasts compared with the standard 6-hour forecasts products. The spatial distribution of CWV are well simulated by the 6-hour forecasts; using the 24-hour forecasts does not degrade this simulation substantially and in many cases improves on the quality. There is also an improved simulation of clear-sky radiation from the 24-hour forecasts compared with the 6-hour forecasts based on comparison with satellite observations and empirical estimates. Further work is required to assess the quality of water vapour simulation by reanalyses over land regions. Over the oceans, it is recommended that 24-hour forecasts of CWV and clear-sky radiation are used in preference to the standard 6-hour forecast products from ERA40

Stratosphere-troposphere transport in a numerical simulation of midlatitude convection

The transport of stratospheric air deep into the troposphere via convection is investigated numerically using the UK Met Office Unified Model. A convective system that formed on 27 June 2004 near southeast England, in the vicinity an upper level potential vorticity anomaly and a lowered tropopause, provides the basis for analysis. Transport is diagnosed using a stratospheric tracer that can either be passed through or withheld from the model’s convective parameterization scheme. Three simulations are performed at increasingly finer resolutions, with horizontal grid lengths of 12, 4, and 1 km. In the 12 and 4 km simulations, tracer is transported deeply into the troposphere by the parameterized convection. In the 1 km simulation, for which the convective parameterization is disengaged, deep transport is still accomplished but with a much smaller magnitude. However, the 1 km simulation resolves stirring along the tropopause that does not exist in the coarser simulations. In all three simulations, the concentration of the deeply transported tracer is small, three orders of magnitude less than that of the shallow transport near the tropopause, most likely because of the efficient dilution of parcels in the lower troposphere.

Linear viscoelasticity from molecular dynamics simulation of entangled polymers

The linear viscoelastic (LVE) spectrum is one of the primary fingerprints of polymer solutions and melts, carrying information about most relaxation processes in the system. Many single chain theories and models start with predicting the LVE spectrum to validate their assumptions. However, until now, no reliable linear stress relaxation data were available from simulations of multichain systems. In this work, we propose a new efficient way to calculate a wide variety of correlation functions and mean-square displacements during simulations without significant additional CPU cost. Using this method, we calculate stress−stress autocorrelation functions for a simple bead−spring model of polymer melt for a wide range of chain lengths, densities, temperatures, and chain stiffnesses. The obtained stress−stress autocorrelation functions were compared with the single chain slip−spring model in order to obtain entanglement related parameters, such as the plateau modulus or the molecular weight between entanglements. Then, the dependence of the plateau modulus on the packing length is discussed. We have also identified three different contributions to the stress relaxation:  bond length relaxation, colloidal and polymeric. Their dependence on the density and the temperature is demonstrated for short unentangled systems without inertia.

An observing system simulation experiment for climate monitoring with GNSS radio occulation data: setup and testbed study

The long-term stability, high accuracy, all-weather capability, high vertical resolution, and global coverage of Global Navigation Satellite System (GNSS) radio occultation (RO) suggests it as a promising tool for global monitoring of atmospheric temperature change. With the aim to investigate and quantify how well a GNSS RO observing system is able to detect climate trends, we are currently performing an (climate) observing system simulation experiment over the 25-year period 2001 to 2025, which involves quasi-realistic modeling of the neutral atmosphere and the ionosphere. We carried out two climate simulations with the general circulation model MAECHAM5 (Middle Atmosphere European Centre/Hamburg Model Version 5) of the MPI-M Hamburg, covering the period 2001–2025: One control run with natural variability only and one run also including anthropogenic forcings due to greenhouse gases, sulfate aerosols, and tropospheric ozone. On the basis of this, we perform quasi-realistic simulations of RO observables for a small GNSS receiver constellation (six satellites), state-of-the-art data processing for atmospheric profiles retrieval, and a statistical analysis of temperature trends in both the “observed” climatology and the “true” climatology. Here we describe the setup of the experiment and results from a test bed study conducted to obtain a basic set of realistic estimates of observational errors (instrument- and retrieval processing-related errors) and sampling errors (due to spatial-temporal undersampling). The test bed results, obtained for a typical summer season and compared to the climatic 2001–2025 trends from the MAECHAM5 simulation including anthropogenic forcing, were found encouraging for performing the full 25-year experiment. They indicated that observational and sampling errors (both contributing about 0.2 K) are consistent with recent estimates of these errors from real RO data and that they should be sufficiently small for monitoring expected temperature trends in the global atmosphere over the next 10 to 20 years in most regions of the upper troposphere and lower stratosphere (UTLS). Inspection of the MAECHAM5 trends in different RO-accessible atmospheric parameters (microwave refractivity and pressure/geopotential height in addition to temperature) indicates complementary climate change sensitivity in different regions of the UTLS so that optimized climate monitoring shall combine information from all climatic key variables retrievable from GNSS RO data.