Friday, December 2, 2011

Weird world of water gets a little weirder with a new anomaly

Pradeep Kumar and H. Eugene Stanley explain that water is one weird substance, exhibiting more than 80 unusual properties, by one count, including some that scientists still struggle to understand. For example, water can exist in all three states of matter (solid, liquid,gas) at the same time. And the forces at its surface enable insects to walk on water and water to rise up from the roots into the leaves of trees and other plants. In another strange turn, scientists have proposed that water can go from being one type of liquid into another in a so-called "liquid-liquid" phase transition, but it is impossible to test this with today's laboratory equipment because these things happen so fast. That's why Kumar and Stanley used to check it out.

They found that when they chilled liquid water in their simulation, its propensity to conduct heat decreases, as expected for an ordinary liquid. But, when they lowered the temperature to about 54 degrees below zero Fahrenheit, the liquid water started to conduct heat even better in the simulation. Their studies suggest that below this temperature, liquid water undergoes sharp but continuous structural changes whereas the local structure of liquid becomes extremely ordered -- very much like ice. These structural changes in lead to increase of heat conduction at lower temperatures. The researchers say that this surprising result supports the idea that water has a liquid-liquid phase transition.

More information: Thermal Conductivity Minimum: A New Water Anomaly, J. Phys. Chem. B, Article ASAP. DOI: 10.1021/jp2051867

We investigate the thermal conductivity of liquid water using computer simulations of the TIP5P model of water. Our simulations show that, in addition to the maximum at high temperatures at constant pressure that it exhibits in experiments, the thermal conductivity also displays a minimum at low temperatures. We find that the temperature of minimum thermal conductivity in supercooled liquid water coincides with the temperature of maximum specific heat. We discuss our results in the context of structural changes in liquid water at low temperatures.

Provided by American Chemical Society (news : web)

Carbon dioxide recycling? 'Diagonal' approach for reductive functionalization of carbon dioxide

“Carbon dioxide is a nontoxic, abundant C1 building block,” says Cantat. “Only a handful of processes using this starting material have been developed, because carbon dioxide is a very stable molecule that can not easily be made to react.” To date, there have been two different approaches for the use of carbon dioxide. According to Cantat, “In the ‘vertical’ approach, the carbon dioxide is reduced, which means that the oxidation state of the carbon atom is reduced by the formal replacement of oxygen with hydrogen. This results in molecules such as methanol or formic acid, which can be converted into fuels.” These products have a higher energy content than carbon dioxide, but only a handful of chemicals can be produced this way.

“In the ‘horizontal’ approach, the carbon atom is functionalized, which means that it forms new bonds to oxygen, nitrogen, or other ”, continues Cantat. “The oxidation state stays the same, the energy content is not increased.” This does not produce fuels, but chemicals that are useful building blocks for chemical syntheses, such as urea.

The French team thus tried a compromise approach, a combination of both methods to make a “diagonal” approach. By their method, the carbon dioxide is both reduced and functionalized in one step. This allows the synthesis of a much greater number of chemicals, directly from CO2.

This reaction requires three things: a reducing agent (e.g. a silane), an organic molecule to be attached to the carbon atom of the (e.g. an amine), and a special catalyst that catalyzes both the reduction and the functionalization. The successful catalyst is a special organic base consisting of a nitrogen-containing ring system. “Variation of the reaction partners should allow us to make a whole series of chemical compounds that are normally obtained from petrochemical feedstocks,” says Cantat, “for example, formamide derivatives, which are important intermediates for both chemical and pharmaceutical industries.”

More information: Thibault Cantat, A Diagonal Approach to Chemical Recycling of Carbon Dioxide: Organocatalytic Transformation for the Reductive Functionalization of CO2, Angewandte Chemie International Edition, … ie.201105516

Provided by Wiley (news : web)

New technique enables study of 'challenging' proteins

The technique, an enhanced form of (NMR) spectroscopy, could enable the structure of a protein to be identified within hours, rather than weeks or months, radically speeding up the process of . The findings are published online in the .

Dr Mark Lorch from the University of Hull, who led the research, explains: " are important targets for the pharmaceutical industry, but they're very difficult to create in large quantities. For some, NMR isn't feasible at all, but even when it is, only small amounts of data can be gained from each small sample, which makes the whole process of identifying the structure very time consuming and expensive.

"Using this technique, we were able to get significant structural data from a small sample of a protein in just 20 hours of NMR time. This is the first time the technique has been shown to work on the size of sample that can be realistically created from any biological protein."

The researchers, from the Universities of Hull, Bristol and Goethe University, used a method known as dynamic nuclear (DNP), which boosts the number of nuclei that can be measured through NMR and so increases the signal picked up from the protein.

Although DNP has been used before on large sample sizes of well-studied proteins, the researchers are the first to show its effectiveness in studying a more challenging protein, opening the door to the study of that are currently inaccessible to conventional NMR.

The study focused on the Sec translocon protein, which transports other proteins either across or into . This process is triggered when a signal peptide called LamB binds with Sec translocon and the researchers wanted to identify structural information on how the two interact. This would have been impossible through traditional NMR, as the signal peptide makes up such a small part of the sample to be studied. However, using DNP to enhance the signal from the peptide, the researchers were able to get significant information in a very short period of time.

Provided by University of Hull

TACC supercomputers help researchers find deeper insight into structure and behavior of protein, DNA and RNA

Analytical ultracentrifugation (AUC) experiments spin samples at very high speeds to study how large molecules such as proteins, DNA and RNA, act in solution. Under the influence of centrifugal forces up to 250,000 times as strong as Earth's gravity, materials undergo sedimentation and diffusion processes over time, revealing aspects of the individual molecules' natures.

These processes are essential measurements for biochemists: a way to understand how molecules behave under physiological solution conditions. And 85 years later, scientists are still finding ways to make the analytic ultracentrifuge more useful.

Unlike traditional microscopy where samples are bound to a microscope grid, or x-ray crystallography where they are locked into a crystal with packing forces that may distort the molecule, AUC experiments preserve the native structures and configurations of molecules. They do this by analyzing molecules in solution, where they can dynamically interact and bind to other molecules, or react to environmental changes such as temperature, ionic strength or pH.

TACC supercomputers help researchers find deeper insight into structure and behavior of protein, DNA and RNA

A van Holde - Weischet analysis providing a differential (green) and integral (red) sedimentation profile for a sedimentation velocity experiment performed on a restriction digest of a DNA fragment. In the integral distribution, the vertical axis indicates the relative concentration of each species, while the horizontal axes indicates the sedimentation coefficient.

"If you don't have a way to measure your molecule in solution, then a lot of this will escape you," said Borries Demeler, associate professor of biochemistry at The University of Texas Health Sciences Center and director of the Center for Analytical Ultracentrifugation of Macromolecular Assemblies (CAUMA). "By studying biological macromolecules in a solution, it is possible to observe reactions, and follow conformational changes."

AUC is also a very versatile tool to study composition. Even trace amounts of impurities can be resolved by AUC, and mixtures can be analyzed to identify molecular weight and shape distributions.

Initially, the analysis of centrifugal experiments was done manually, but with the emergence of computers and sensors in the 1960s, more precise ways of assessing experimental results were developed. Today's optical systems can follow sedimenting and diffusing molecules by detecting ultraviolet and visible absorption, the refractive index, and fluorescence emission. The signals are captured digitally to allow them to be analyzed by computer.

For more than two decades, Demeler has worked at the intersection of the physical (spinning samples) and the virtual (supercomputer simulations), investigating new methods and developing software to help researchers make the most of their AUC experiments.

As the director of CAUMA, Demeler works with hundreds of investigators around the world, including biophysicists studying the structure and function of biological macromolecules and assemblies, material scientists trying to make more efficient solar cells, and the pharmaceutical industry evaluating the stability of their formulations. As a collaborator in many research projects, he is continually challenged by new research questions and enjoys the interactions with many fascinating scientists.

His largest impact, however, is felt through the creation of the UltraScan software package, and the development of the UltraScan LIMS portal through which researchers analyze their experimental data over the web using advanced computing methods and systems.

"I started writing the very first version of UltraScan using BASIC on a 286 PC back in 1988," Demeler recalled, "and it's gone through many iterations. "

In 2004, Demeler and his colleague, Emre Brookes, began parallelizing the code so it could run on large-scale computer clusters. This dramatically sped up the rate at which samples could be analyzed. It also enabled the researchers to develop high-resolution analysis methods and address an entirely new class of research questions that widened the application of the AUC method.

TACC supercomputers help researchers find deeper insight into structure and behavior of protein, DNA and RNA

A single scan of a sedimentation velocity experiment with semiconducting nanoparticles collected with a novel multiwavelength detector. This novel detector can resolve not only composition by hydrodynamic separation, but also by spectral decomposition, and is developed in Dr. Helmut C?lfen's laboratory at the University of Konstanz in Germany.

UltraScan doesn't just allow researchers to measure the diffusion and sedimentation processes; it decodes the meaning of these processes and uncovers hidden characteristics of the sample.

"We often don't know what really is in a solution provided by a collaborator, and we need to get the most out of our analysis," Demeler explained. "To fit the data, we simulate many different components that may be in the solution, and ask the question, ‘How much of each component is present in the actual experiment?'"

This process can be done on a regular computer, but the answers that such a process generates lack the resolution required for clinical or industrial investigations, or simply take too long to complete.

"To squeeze out the last drop of information, you need to go through quite a bit more computational expense," Demeler said. "This is where we kick in with our methods."

UltraScan's numerical methods extract noise, narrow the parameter space, compare multiple experiments, and determine the uncertainty of the result.

While some analyses are performed on a small development cluster in Demeler's lab, the capacity is insufficient to address the most challenging problems, and to satisfy all of the demand for analysis among a growing international group of AUC users. Instead, Demeler relies on the computing systems of the National Science Foundation funded Extreme Science and Engineering Discovery Environment (XSEDE), the most powerful, and robust collection of integrated advanced digital resources and services in the world.

Demeler's simulations use anywhere between 40 and 14,000 processors simultaneously, speeding up the analytic processing by as much as 10,000 times. In 2010-2011, Demeler used 3.5 million computing hours on the Ranger and Lonestar supercomputers at the Texas Advanced Computing Center (TACC) to perform simulations for the open science community.

"It's not just reserved for biochemists and biophysicists," Demeler said. "We might work with a clinician, perform measurements for materials science, or measure the binding strength of a new drug to its target."

Demeler pointed to a recent example of work he is doing with researchers in Germany characterizing fluorescent nanoparticles made out of cadmium telluride crystals for use in solar panels. Using a new detector developed by a collaborator at the Max Planck Institute, he was able to not only measure the hydrodynamic properties, but also observe their individual absorption spectra, and correlate absorbance properties with particle size.

TACC supercomputers help researchers find deeper insight into structure and behavior of protein, DNA and RNA

2-dimensional spectrum - Monte Carlo analysis of a sedimentation velocity experiment. In this experiment two interacting proteins (A and B) were titrated against each other, resulting in a non-globular complex. In the upper left, protein A is shown to generate several globular oligomers. Addition of protein B results in the appearance of a non-globular peak (upper right). An increasing amount of protein B causes an increase of the AB complex (lower left). At the highest concentration of protein B, the lowest molecular weight form of the globular species has completely disappeared, and been converted into the non-globular species. This work was performed in collaboration with Bettie Sue Master's laboratory at UTHSCSA.

Whether the application is nanoparticles for industry or biomarkers in blood, AUC together with UltraScan is an incredibly useful tool. But creating the software and algorithms wasn't the final step. Many potential users of AUC and UltraScan are not computer scientists, and Demeler believed a fear of the command line interface would prevent them from using the software.

"To get people to adopt this technology, you have to make it easy for them," he said. "It needs to be extremely robust, user-friendly and intuitive."

Through an Advanced Support for TeraGrid Applications (ASTA) grant from the NSF, staff at Indiana University helped Demeler develop a web-based gateway where researchers log in, access their data, and submit jobs as if they were running a very simple web application.

"The user only has to be familiar with the basic analysis procedure and a web browser; familiarity with Unix supercomputing is not required," Demeler said. "Our users really like this approach."

Eighty-five years after its inception, the evolution of the analytic ultracentrifuge continues. The latest challenge involves finding ways to integrate AUC results with results from other solution methods.

Demeler and Brookes are developing an integrated system combining molecular dynamics with hydrodynamic and small angle scattering simulations to screen a large variety of structural conformations against experimental data. This will give a large pool of researchers new insight into the structure and function of molecules under study.

"The knowledge obtained should enhance our understanding of biomolecular processes, including disease processes, which can lead to improved prevention and treatment," said Emre Brookes. "None of this would be feasible without the vast computational resources available through XSEDE."

Demeler and Brookes' long-term dream is to create a way to integrate all known observational methods — including x-ray crystallography, nuclear magnetic resonance imaging, and calorimetry — to see more deeply than we currently do, without losing sight of the natural conditions under which molecules exist.

"It's like taking a picture of an object from many different angles, and every time you take a picture you see something else that adds to the whole," Demeler said. "By combining them all, the new picture will tell you something you didn't know before."

More information: To read more about the challenges of biochemistry and the role of AUC in protein study, see Demeler's recent commentary in the June 2011 edition of Nature Chemical Biology.

The story is courtesy of Faith Singer-Villalobos @ Texas Advanced Computing Center (TACC).

Provided by University of Texas at Austin (news : web)

Flexible rack systems sort molecules

Enantiomers are pairs of molecules built in a mirror-inverted manner. They differ from each other like a left and a right glove. This property of the molecules that is referred to as chirality is of particular relevance to biosciences and pharmaceutics. "While many, especially smaller, molecules like or are not chiral, many biologically relevant molecules, such as tartaric acid have this property," explains Professor Christof Wöll, Head of the KIT Institute of Functional Interfaces (IFG). For many pharmaceutical agents, only one of both enantiomers is desired for the effective molecules being able to dock to certain structures in the body.

In contrast to conventional methods, the process developed by the team of researchers directed by Professor Wöll, Professor Roland Fischer from the Chair for Inorganic Chemistry II of RUB, and Humboldt scholar Bo Liu (KIT and RUB) allows for a more rapid and, hence, cheaper separation of enantiomers. It is based on novel molecular frameworks (MOFs) that can be grown on solid . These porous coatings that are also referred to as SURMOFs are produced by an epitaxy process specifically developed by the researchers. Instead of heating the solution mixtures produced from the initial substances, modified substrates are immersed alternately in the solutions of the initial substances. "In this way, the molecular layers are assembled one after the other comparable to a rack system," explains Roland Fischer. These molecular rack systems anchored to the surfaces can be functionalized for various applications.

The enantiomers are separated by chiral organic molecules that are the linkers or struts of the rack systems. Thanks to their enantiopure structure, these coatings retain one of both enantiomers. In their contribution that was also selected for the title photo of the journal Angewandte Chemie, the scientists describe the separation of the enantiomer molecules (2R, 5R)-2,5-hexanediol (R-HDO) and (2S, 5S)-2,5-hexanediol (S-HDO). Future work will be aimed at increasing the mesh width of the porous structures in order to test the method for larger used as pharmaceuticals. "Pharmaceutical substances are two or more nanometers in size and, hence, larger than hexanediol. The development of surface-attached networks with such large structures is a big challenge," explains Professor Wöll.

It is a particular advantage of SURMOFs that the efficiency of enantiomer separation can be measured rapidly and precisely. With the help of quartz crystal microbalances, it was demonstrated that surface-anchored molecular framework structures reach excellent separation efficiencies already. "The SURMOFs as a new material have an enormous potential for use in pharmaceutical industry," explains Professor Jürgen Hubbuch, holder of the Chair for Molecular Separation Engineering (MAB) and Spokesman of the KIT Competence Field of Biotechnology.

More information: Bo Liu, Osama Shekhah, Hasan K. Arslan, Jinxuan Liu, Christof Wöll, and Roland A Fischer. Enantiomerenreine Dünnschichten auf der Basis Metall-organischer Gerüste: orientiertes Wachstum von SURMOFs und enantioselektive Adsorption (Enantiomer-pure thin layers on the basis of metal-organic frameworks: Oriented growth of SURMOFs and enantioselective adsorption). Angewandte Chemie. DOI: 10.1002/ange.201104240

Provided by Helmholtz Association of German Research Centres (news : web)