Experimental Heat-Bath Cooling of Spins

Algorithmic cooling (AC) is a method to purify quantum systems, such as ensembles of nuclear spins, or cold atoms in an optical lattice. When applied to spins, AC produces ensembles of highly polarized spins, which enhance the signal strength in nuclear magnetic resonance (NMR). According to this cooling approach, spin-half nuclei in a constant magnetic field are considered as bits, or more precisely, quantum bits, in a known probability distribution. Algorithmic steps on these bits are then translated into specially designed NMR pulse sequences using common NMR quantum computation tools. The $algorithmic$ cooling of spins is achieved by alternately combining reversible, entropy-preserving manipulations (borrowed from data compression algorithms) with $selective$ $reset$, the transfer of entropy from selected spins to the environment. In theory, applying algorithmic cooling to sufficiently large spin systems may produce polarizations far beyond the limits due to conservation of Shannon entropy. Here, only selective reset steps are performed, hence we prefer to call this process "heat-bath" cooling, rather than algorithmic cooling. We experimentally implement here two consecutive steps of selective reset that transfer entropy from two selected spins to the environment. We performed such cooling experiments with commercially-available labeled molecules, on standard liquid-state NMR spectrometers. Our experiments yielded polarizations that $bypass$ $Shannon's$ $entropy$-$conservation$ $bound$, so that the entire spin-system was cooled. This paper was initially submitted in 2005, first to Science and then to PNAS, and includes additional results from subsequent years (e.g. for resubmission in 2007). The Postscriptum includes more details.Comment: 20 pages, 8 figures, replaces quant-ph/051115

Protein folding on the ribosome studied using NMR spectroscopy

NMR spectroscopy is a powerful tool for the investigation of protein folding and misfolding, providing a characterization of molecular structure, dynamics and exchange processes, across a very wide range of timescales and with near atomic resolution. In recent years NMR methods have also been developed to study protein folding as it might occur within the cell, in a de novo manner, by observing the folding of nascent polypeptides in the process of emerging from the ribosome during synthesis. Despite the 2.3 MDa molecular weight of the bacterial 70S ribosome, many nascent polypeptides, and some ribosomal proteins, have sufficient local flexibility that sharp resonances may be observed in solution-state NMR spectra. In providing information on dynamic regions of the structure, NMR spectroscopy is therefore highly complementary to alternative methods such as X-ray crystallography and cryo-electron microscopy, which have successfully characterized the rigid core of the ribosome particle. However, the low working concentrations and limited sample stability associated with ribosome-nascent chain complexes means that such studies still present significant technical challenges to the NMR spectroscopist. This review will discuss the progress that has been made in this area, surveying all NMR studies that have been published to date, and with a particular focus on strategies for improving experimental sensitivity

New experimental and theoretical tools for studying protein systems with elements of structural disorder

Disordered proteins are one class of proteins which do not possess well-folded three-dimensional structures as their native conformations. Many eukaryotic proteins have been found to be fully disordered or contain certain disordered regions. Disordered proteins usually display several characteristic properties, such as increased motional freedom and the conformational heterogeneity caused by that. The elements of structural disorder are commonly involved in many important biological functions and are implicated in many diseases. Therefore, the study of disordered proteins has become one of the most important research topics in recent years. This thesis presents results from three different research projects; the common feature is that all systems being studied contain varying amount of structural disorder. Most results have been obtained based on experimental nuclear magnetic resonance (NMR) studies and molecular dynamics (MD) simulations. Both are among the most popular biophysical techniques for studying molecular dynamics. The first project investigates the relationship between domain cooperativity and residual dipolar coupling (RDC) parameters based on a series of two-domain chimera proteins with disordered linkers. Many eukaryotic proteins contain multiple domains and their biological functions are closely related to the property of domain cooperativity, which is often regulated by the linker region. Therefore it is necessary to develop suitable tools to characterize linker region properties in order to better understand biological functions of multidomain proteins. The second project is about the development of NMR pulse sequences for studying disordered proteins. Two new NMR pulse sequences, PD-CPMG and CP-HISQC, have been developed. Both experiments are well suited for studying intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs) under physiological conditions. These two experiments produce higher precision for 15N R2 rates measurement or higher sensitivity in 1H– 15N HSQC spectra respectively. Besides, they also show many advantages over most other existing experiments for studying IDPs. The last project is about protein-peptide encounter complex study based on Crk-Sos model system. The ten-residue Sos peptide serves as a minimal model for disordered proteins. Encounter complex is an important type of intermediate state formed during many protein interactions. Such complexes are usually characterized by a large amount of motional freedom and conformational heterogeneity. Therefore their properties are considerably different from tight-binding complexes which are more commonly studied. Although it is usually quite difficult to study encounter complexes using standard biophysical techniques, in this project we have successfully characterized structural and dynamic properties of Crk-Sos electrostatic encounter complex with a combination of MD simulations and experimental NMR approaches. It can be directly seen from the structural model based on MD trajectories that Sos peptide in the encounter complex remains highly dynamic, sampling large area on the surface of Crk N-SH3 domain. Such strategy can also be utilized for studying many other encounter complexes involving disordered proteins or peptide

Collective exchange processes reveal an active site proton cage in bacteriorhodopsin

Proton translocation across membranes is vital to all kingdoms of life. Mechanistically, it relies on characteristic proton flows and modifications of hydrogen bonding patterns, termed protonation dynamics, which can be directly observed by fast magic angle spinning (MAS) NMR. Here, we demonstrate that reversible proton displacement in the active site of bacteriorhodopsin already takes place in its equilibrated dark-state, providing new information on the underlying hydrogen exchange processes. In particular, MAS NMR reveals proton exchange at D85 and the retinal Schiff base, suggesting a tautomeric equilibrium and thus partial ionization of D85. We provide evidence for a proton cage and detect a preformed proton path between D85 and the proton shuttle R82. The protons at D96 and D85 exchange with water, in line with ab initio molecular dynamics simulations. We propose that retinal isomerization makes the observed proton exchange processes irreversible and delivers a proton towards the extracellular release site

Shifty protons and wandering electrons

Møller-Plesset second order perturbation theory (MP2) is one of the most widely used electron correlation methods in computational chemistry. The rising cost of computing demands that computational chemists develop novel cost-saving strategies to reduce the time and energy associated with the most widely used methods in the field. Multiple studies are presented evaluating the effects of two particular strategies (dynamic voltage and frequency scaling and oversubscription) when used with specific MP2 algorithms. Additionally, a collection of experimental collaborations is presented covering a wide range of chemical topics, including organic synthesis, stereochemistry of 1,2-masked diols, nuclear magnetic resonance characterization of silicon nanocrystals, and inorganic catalysis involving cobalt

Online Tensor Methods for Learning Latent Variable Models

We introduce an online tensor decomposition based approach for two latent variable modeling problems namely, (1) community detection, in which we learn the latent communities that the social actors in social networks belong to, and (2) topic modeling, in which we infer hidden topics of text articles. We consider decomposition of moment tensors using stochastic gradient descent. We conduct optimization of multilinear operations in SGD and avoid directly forming the tensors, to save computational and storage costs. We present optimized algorithm in two platforms. Our GPU-based implementation exploits the parallelism of SIMD architectures to allow for maximum speed-up by a careful optimization of storage and data transfer, whereas our CPU-based implementation uses efficient sparse matrix computations and is suitable for large sparse datasets. For the community detection problem, we demonstrate accuracy and computational efficiency on Facebook, Yelp and DBLP datasets, and for the topic modeling problem, we also demonstrate good performance on the New York Times dataset. We compare our results to the state-of-the-art algorithms such as the variational method, and report a gain of accuracy and a gain of several orders of magnitude in the execution time.Comment: JMLR 201

Band-selective hetero- and homonuclear cross-polarization using trains of shaped pulses

The performance of solution cross-polarization using trains of shaped pulses on two channels is investigated by computer simulation and experiment. It is determined that a Waltz modulation pattern of Gaussian pulses of individual flip angles of 225°, issued to two coupled spins simulatneously, yields excellent coherence transfer with good phasing behavior. Simulations and experimental verification were carried out for both heteronuclear cross-polarization between two restricted areas (e.g. 1 H α − 13 C α ) and for homonuclear cross-polarization between two spectral regions (e.g. 13 CO− 13 C α ). It is shown that shaped cross-polarization behaves as pure heteronuclear cross-polarization when the two radiofrequency (rf) fields are far apart, while it behaves in some aspects analogous to homonuclear cross-polarization when the two rf fields approach each other. The novel coherence-transfer sequence, referred to as ‘cosine-modulated shaped Waltz’ (CSW), was implemented in a 3D (H)C(CCO)NH experiment using an 18-kDa isotopically labeled protein.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43054/1/10858_2004_Article_BF00211161.pd

Three-dimensional phase-field study of crack-seal microstructures - insights from innovative post-processing techniques

Numerical simulations of vein evolution contribute to a better understanding of processes involved in their formation and possess the potential to provide invaluable insights into the rock deformation history and fluid flow pathways. The primary aim of the present article is to investigate the influence of a “realistic” boundary condition, i.e. an algorithmically generated “fractal” surface, on the vein evolution in 3-D using a thermodynamically consistent approach, while explaining the benefits of accounting for an extra dimensionality. The 3-D simulation results are supplemented by innovative numerical post-processing and advanced visualization techniques. The new methodologies to measure the tracking efficiency demonstrate the importance of accounting the temporal evolution; no such information is usually accessible in field studies and notoriously difficult to obtain from laboratory experiments as well. The grain growth statistics obtained by numerically post-processing the 3-D computational microstructures explain the pinning mechanism which leads to arrest of grain boundaries/multi-junctions by crack peaks, thereby, enhancing the tracking behavior