Building Water Models, A Different Approach

Simplified, classical models of water are an integral part of atomistic molecular simulations, especially in biology and chemistry where hydration effects are critical. Yet, despite several decades of effort, these models are still far from perfect. Presented here is an alternative approach to constructing point charge water models - currently, the most commonly used type. In contrast to the conventional approach, we do not impose any geometry constraints on the model other than symmetry. Instead, we optimize the distribution of point charges to best describe the "electrostatics" of the water molecule, which is key to many unusual properties of liquid water. The search for the optimal charge distribution is performed in 2D parameter space of key lowest multipole moments of the model, to find best fit to a small set of bulk water properties at room temperature. A virtually exhaustive search is enabled via analytical equations that relate the charge distribution to the multipole moments. The resulting "optimal" 3-charge, 4-point rigid water model (OPC) reproduces a comprehensive set of bulk water properties significantly more accurately than commonly used rigid models: average error relative to experiment is 0.76%. Close agreement with experiment holds over a wide range of temperatures, well outside the ambient conditions at which the fit to experiment was performed. The improvements in the proposed water model extend beyond bulk properties: compared to the common rigid models, predicted hydration free energies of small molecules in OPC water are uniformly closer to experiment, root-mean-square error < 1kcal/mol

Investigations on Electrochemical Micro Drilling of Nickel Alloy using Taguchi based Grey Approach

Inconel 600 is the nickel based super alloy which is employed in numerous engineering applications like gas turbine blades, turbochargers and heat exchangers etc. However, it is very difficult to machine due to its high strength and poor thermal diffusion. Conventional machining methods of these materials may result in decreased life time. An electrochemical machining is an advanced non-traditional technique which is suitable for machining hard material, strenuous materials and Intricate shapes. In this paper, electrochemical micro drilling (ECMD) on Inconel 600 material is investigated. The experiments are devised and analyzed using Taguchi’s L18 orthogonal array and Grey relational analysis (GRA). Analysis of variance (ANOVA) has been implemented to find out the significance of electrochemical micro drilling parameters on the performance characteristics

Point Charges Optimally Placed to Represent the Multipole Expansion of Charge Distributions

We propose an approach for approximating electrostatic charge distributions with a small number of point charges to optimally represent the original charge distribution. By construction, the proposed optimal point charge approximation (OPCA) retains many of the useful properties of point multipole expansion, including the same far-field asymptotic behavior of the approximate potential. A general framework for numerically computing OPCA, for any given number of approximating charges, is described. We then derive a 2-charge practical point charge approximation, PPCA, which approximates the 2-charge OPCA via closed form analytical expressions, and test the PPCA on a set of charge distributions relevant to biomolecular modeling. We measure the accuracy of the new approximations as the RMS error in the electrostatic potential relative to that produced by the original charge distribution, at a distance the extent of the charge distribution–the mid-field. The error for the 2-charge PPCA is found to be on average 23% smaller than that of optimally placed point dipole approximation, and comparable to that of the point quadrupole approximation. The standard deviation in RMS error for the 2-charge PPCA is 53% lower than that of the optimal point dipole approximation, and comparable to that of the point quadrupole approximation. We also calculate the 3-charge OPCA for representing the gas phase quantum mechanical charge distribution of a water molecule. The electrostatic potential calculated by the 3-charge OPCA for water, in the mid-field (2.8 Å from the oxygen atom), is on average 33.3% more accurate than the potential due to the point multipole expansion up to the octupole order. Compared to a 3 point charge approximation in which the charges are placed on the atom centers, the 3-charge OPCA is seven times more accurate, by RMS error. The maximum error at the oxygen-Na distance (2.23 Å ) is half that of the point multipole expansion up to the octupole order

Hot Upset Studies on Sintered (Al–TiO₂–Gr) Powder Metallurgy Hybrid Composite

Алюминиевые гибридные композиты Al+5%TiO₂, Al+5%TiO₂+2%Gr и Al+5%TiO₂+4%Gr из измельченных на грануляторе порошков синтезированы методом порошковой металлургии. Исследования методами сканирующей электронной микроскопии и энергодисперсионной рентгеновской спектроскопии показали, что упрочняющие добавки по объему образцов распределяются равномерно. Испытания на горячую осадку образцов, нагретых до 450°C, проведены с подробным изучением характеристик уплотнения и деформирования путем корреляции истинного осевого напряжения с истинной осевой деформацией, продольной деформацией и теоретической плотностью. Показано, что генерируемые в процессе горячей осадки напряжения увеличиваются при добавке графита в композит Al TiO₂ и диоксида титана в Al без упрочняющих добавок. Выполнен анализ микроструктуры образцов после горячей осадки.Алюмінієві гібридні композити Al+5%TiO₂, Al+5%TiO₂+2%Gr й Al+5%TiO₂+4%Gr із подрібнених на грануляторі порошків синтезовані методом порошкової металургії. Дослідження методами сканувальної електронної мікроскопії та енергодисперсійної рентгенівської спектроскопії показали, що зміцнювальні домішки по об єму зразка розподіляються рівномірно. Випробування на гарячу осадку нагрітих до 450°С зразків проведено з детальним вивченням характеристик ущільнення і деформування шляхом кореляції істинного осьового напруження з істинною осьовою деформацією, поздовжньою деформацією і теоретичною щільністю. Показано, що генеруючі в процесі гарячої осадки напруження збільшуються при додатку графіту в композит Al TiO₂ і диоксиду титану в Al без зміцнювальних домішок. Виконано аналіз мікроструктури зразка після гарячої осадки

Accelerated Short-Term Techniques to Evaluate Corrosion in TiC Reinforced AA6063 Composites

AA6063-TiC composites have several weight percentages up to 9 wt. % were fabricated by using stir casting route method. The effects of the weight percentage of TiC particles on the microstructures and corrosion behavior of AA6063-TiC composites were studied. The results revealed that the AA6063-TiC composites exhibited higher density than the AA6063 matrix. The accelerated corrosion tests of AA6063-TiC composites in 3.5 wt. % NaCl aqueous solution at room temperature, the AA6063-TiC composites have better corrosion resistance than the AA6063 matrix. Increasing the weight percentage of the TiC particles to reduces the corrosion rate of the AA6063-TiC composites. In this process corrosion rate of 0.4402 mm/year for AA6063 matrix, 0.3891 mm/year for 3 wt. % , 0.3568 mm/year for 6 wt. % and 0.3062 mm/year for 9 wt. % of TiC particles respectively. The poor corrosion resistance of the composites can be attributed to the galvanic effects between the AA6063 matrix and TiC reinforcement

Phugoid motion for grazing-entry trajectories at near-circular speeds

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77023/1/AIAA-26742-801.pd

A Computational Assay of Estrogen Receptor alpha Antagonists Reveals the Key Common Structural Traits of Drugs Effectively Fighting Refractory Breast Cancers

Somatic mutations of the Estrogen Receptor alpha (ER alpha) occur with an up to 40% incidence in ER sensitive breast cancer (BC) patients undergoing prolonged endocrine treatments. These polymorphisms are implicated in acquired resistance, disease relapse, and increased mortality rates, hence representing a current major clinical challenge. Here, multi-microseconds (12.5 mu s) molecular dynamics simulations revealed that recurrent ER alpha. polymorphisms (i.e. L536Q, Y5375, Y537N, D538G) (mER alpha) are constitutively active in their apo form and that they prompt the selection of an agonist (active)-like conformation even upon antagonists binding. Interestingly, our simulations rationalize, for thefirst time, the efficacy profile of (pre)clinically used Selective Estrogen Receptor Modulators/Downregulators (SERMs/SERDs) against these variants, enlightening, at atomistic level of detail, the key common structural traits needed by drugs able to effectively fight refractory BC types. This knowledge represents a key advancement for mechanism-based therapeutics targeting resistant ER alpha isoforms, potentially allowing the community to move a step closer to 'precision medicine' calibrated on patients' genetic profiles and disease progression

Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca 2+ -binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp-Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus.We gratefully acknowledge Karsta Barnekow and Kristine Sievert-Giermann, for technical assistance and Lothar Petruschka for in silico analysis (all Dept. of Genetics, University of Greifswald). We are further grateful to the staff from SLS synchrotron beamline for help in data collection. This work was supported by grants from the Deutsche Forschungsgemeinschaft DFG GRK 1870 (to SH) and the Spanish Ministry of Economy and Competitiveness (BFU2014-59389-P to JAH, CTQ2014-52633-P to MB and SAF2012-39760-C02-02 to FG) and S2010/BMD- 2457 (Community of Madrid to JAH and FG).Peer Reviewe

Delivering 21st century Antarctic and Southern Ocean science

The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together

Mechanical unfolding of proteins – comparative non-equilibrium molecular dynamics study

Mechanical signals regulate functions of mechanosensitive proteins by inducing structural changes that are determinant for force-dependent interactions. Talin is a focal adhesion protein that is known to extend under mechanical load, and it has been shown to unfold via intermediate states. Here, we compared different nonequilibrium molecular dynamics (MD) simulations to study unfolding of the talin rod. We combined boxed MD (BXD), steered MD, and umbrella sampling (US) techniques and provide free energy profiles for unfolding of talin rod subdomains. We conducted BXD, steered MD, and US simulations at different detail levels and demonstrate how these different techniques can be used to study protein unfolding under tension. Unfolding free energy profiles determined by BXD suggest that the intermediate states in talin rod subdomains are stabilized by force during unfolding, and US confirmed these results