Acetylcholinesterase, with an active site located at the bottom of a narrow and deep gorge, provides a striking example of enzymes with buried active sites. Recent molecular dynamics simulations ...showed that reorientation of five aromatic rings leads to rapid opening and closing of the gate to the active site. In the present study the molecular dynamics trajectory is used to quantitatively analyze the effect of the gate on the substrate binding rate constant. For a 2.4- angstrom probe modeling acetylcholine, the gate is open only 2.4% of the time, but the quantitative analysis reveals that the substrate binding rate is slowed by merely a factor of 2. We rationalize this result by noting that the substrate, by virtue of Brownian motion, will make repeated attempts to enter the gate each time it is near the gate. If the gate is rapidly switching between the open and closed states, one of these attempts will coincide with an open state, and then the substrate succeeds in entering the gate. However, there is a limit on the extent to which rapid gating dynamics can compensate for the small equilibrium probability of the open state. Thus the gate is effective in reducing the binding rate for a ligand 0.4 angstrom bulkier by three orders of magnitude. This relationship suggests a mechanism for achieving enzyme specificity without sacrificing efficiency.
Liquefied natural gas (LNG) has an increasingly important role in the global natural gas market. Global demand for natural gas will grow over the coming years. LNG is transported by ships to ...unloading points at the storage terminals. During the LNG storage processes some part of LNG evaporates into gas phase. Evaporated LNG is called Boil-off gas (BOG). LNG is stored at cryogenic temperatures. Heat flow has an impact on evaporation process. It indicates there is continuous boil-off of small fraction or portion of LNG due to warming during storage process. This boil-off gas is generated primarily due to heat flow from the ambient air through tank insulation, unloading and recirculation-line insulation. Vaporization process causes changes in the composition of stored Liquefied Natural Gas. Increased vaporization process may negatively affect the stability and safety of the LNG storage process. Rate of vaporization (boil off rate) should be precisely determined. For these reasons different calculation models to determine the LNG boil-off rate are shown in this paper, also there are presented some boil off rate calculation results for different Liquefied Natural Gas compositions. Obtained results show that Boil-off rate is higher for LNG composition which contains nitrogen. Due to lower bubble temperature nitrogen evaporates first from the LNG, it causes significant LNG density drop in surface layer in storage tank. Difference of densities in surface and bottom layer of stored LNG may cause the stratification process and consequently affect the stability of storage process (possibility of roll-over phenomenon).
We have studied the dynamic properties of acetylcholinesterase dimer from Torpedo californica liganded with tacrine (AChE−THA) in solution using molecular dynamics. The simulation reveals ...fluctuations in the width of the primary channel to the active site that are large enough to admit substrates. Alternative entries to the active site through the side walls of the gorge have been detected in a number of structures. This suggests that transport of solvent molecules participating in catalysis can occur across the porous wall, contributing to the efficiency of the enzyme.
The RHIC and ATLAS Computing Facility (RACF) at Brookhaven Lab is a dedicated data center serving the needs of the RHIC and US ATLAS community. Since it began operations in the mid-1990's, it has ...operated continuously with few unplanned downtimes. In the past 15 months, Brookhaven Lab has been affected by two hurricanes and a record-breaking snowstorm. In this presentation, we discuss lessons learned regarding (natural or man-made) disaster preparedness, operational continuity, remote access and safety protocols, including overall operational procedures developed as a result of these recent events.
Liquefied natural gas (LNG) has an important role in the global industry and energy balance. The use of this energy carrier has been increasing for last decades. The broad development of the LNG ...sector has been noticeable in the search for new supply directions by natural gas customers. An important option to transport the gas is to convert it into liquid natural gas (LNG) and convey it using insulated LNG tankers. At receiving terminals, the LNG is unloaded into storage tanks and then pumped for the required pressure, vaporized and compressed for final pipeline transmission to natural gas pipeline system. The LNG production process consumes a considerable amount of energy. This energy is stored in LNG as cold energy. At an unloading terminal, LNG is evaporated into gas phase at ambient temperature before pumping into the natural gas transmission system. Seawater or ambient airare commonly used for the regasification process of the LNG. In process of regasification the large part of energy stored in LNG may be recovered and used for electricity generation. In the presented paper a general analysis of the various thermodynamic schemes proposed for power production from regasification has been made. Direct expansion cycle, Rankine cycle and Brayton cycle are analyzed in presented case.
The PanDA distributed production and analysis system has been in production use for ATLAS data processing and analysis since late 2005 in the US, and globally throughout ATLAS since early 2008. Its ...core architecture is based on a set of stateless web services served by Apache and backed by a suite of MySQL databases that are the repository for all PanDA information: active and archival job queues, dataset and file catalogs, site configuration information, monitoring information, system control parameters, and so on. This database system is one of the most critical components of PanDA, and has successfully delivered the functional and scaling performance required by PanDA, currently operating at a scale of half a million jobs per week, with much growth still to come. In this paper we describe the design and implementation of the PanDA database system, its architecture of MySQL servers deployed at BNL and CERN, backup strategy and monitoring tools. The system has been developed, thoroughly tested, and brought to production to provide highly reliable, scalable, flexible and available database services for ATLAS Monte Carlo production, reconstruction and physics analysis.
Brownian dynamics simulations of the encounter kinetics between the active site of the wild-type and Glu199 mutant of Torpedo californica acetylcholinesterase (TcAChE) with a charged substrate were ...performed. In addition, ab initio quantum chemical calculations using the 3-21G basis set were undertaken to probe the energetics of the transformation of the Michaelis complex into a covalently bound tetrahedral intermediate using various models of the wild-type and Glu199Gln mutant active sites. The quantum calculations predicted about a factor of 32 reduction in the rate of formation of the tetrahedral intermediate upon the Glu199Gln mutation and showed that the Glu199 residue located in the proximity of the enzyme active triad boosts AChE's activity in a dual fashion: (1) by increasing the encounter rate due to the favorable modification of the electric field inside the enzyme reaction gorge and (2) by stabilization of the transition state for the first chemical step of catalysis. Our calculations also demonstrate the critical role of the oxyanion hole in stabilization of the tetrahedral intermediate and suggests that a charge relay mechanism may operate in the Glu199Gln mutant AChE as opposed to a general base mechanism as in the wild-type enzyme.
A recent experimental study of human acetylcholinesterase has shown that the mutation of surface acidic residues has little effect on the rate constant for hydrolysis of acetylthiocholine. It was ...concluded, on this basis, that the reaction is not diffusion controlled and that electrostatic steering plays only a minor role in determining the rate. Here we examine this issue through Brownian dynamics simulations on Torpedo californica acetylcholinesterase in which the surface acidic residues homologous with those mutated in the human enzyme are artificially neutralized. The computed effects of the mutations on the rate constants reproduce quite well the modest effects of the mutations upon the measured encounter rates. Nonetheless, the electrostatic field of the enzyme is found to increase the rate constants by about an order of magnitude in both the wild type and the mutants. We therefore conclude that the mutation experiments do not disprove that electrostatic steering substantially affects the catalytic rate of acetylcholinesterase.
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