Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized

Understanding protein structure is of crucial importance in science, medicine and biotechnology. For about two decades, knowledge based potentials based on pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been center stage in the prediction and design of protein structure and the simulation of protein folding. However, the validity, scope and limitations of these potentials are still vigorously debated and disputed, and the optimal choice of the reference state -- a necessary component of these potentials -- is an unsolved problem. PMFs are loosely justified by analogy to the reversible work theorem in statistical physics, or by a statistical argument based on a likelihood function. Both justifications are insightful but leave many questions unanswered. Here, we show for the first time that PMFs can be seen as approximations to quantities that do have a rigorous probabilistic justification: they naturally arise when probability distributions over different features of proteins need to be combined. We call these quantities reference ratio distributions deriving from the application of the reference ratio method. This new view is not only of theoretical relevance, but leads to many insights that are of direct practical use: the reference state is uniquely defined and does not require external physical insights; the approach can be generalized beyond pairwise distances to arbitrary features of protein structure; and it becomes clear for which purposes the use of these quantities is justified. We illustrate these insights with two applications, involving the radius of gyration and hydrogen bonding. In the latter case, we also show how the reference ratio method can be iteratively applied to sculpt an energy funnel. Our results considerably increase the understanding and scope of energy functions derived from known biomolecular structures

Relationship Between the Thermodynamic Parameters, Structure, and Anticorrosion Properties of Al-Zr-Ni-Fe-Y Alloys

The influence of the chemical composition on the crystallization process, amorphous phase formation, and the anticorrosion properties of Al-Zr-Ni-Fe-Y alloys are presented. To reduce the number of experiments, a thermodynamic approach was applied in which the entropy and Gibbs free energy of representative alloys were optimized. The low glass-forming ability of Al-Zr-Ni-Fe-Y alloy systems was related to the crystallization of the Al3Zr phase from the melt. The structural analysis showed that phases containing Ni and Fe, such as Al19Ni5Y3, Al10Fe2Y, and Al23Ni6Y4, played a key role in the formation of amorphous alloys. According to this, the simultaneous addition of Ni/Fe and Y is important to prevent the crystallization of Al-based alloys in the melt. The formation of an amorphous phase in Al80Zr5Ni5Fe5Y5 alloys and the complete amorphization of Al85Ni5Fe5Y5 alloys were responsible for the high corrosion resistance compared with fully crystalline alloys. Moreover, the addition of Y had a significant impact on the anticorrosion properties. The XPS results showed that the alloys tended to form a passive Al2O3 and Y2O3 layer on the surface

Repeatability of tensile properties in high pressure die-castings of an Al-Mg-Si-Mn alloy

© 2015 The Korean Institute of Metals and Materials and Springer Science+Business Media Dordrecht High pressure die-castings of an Al-Mg-Si-Mn alloy have been assessed in terms of the repeatability of the mechanical properties including yield strength, ultimate tensile strength and elongation by the normal standard deviations method and by the Weibull statistical model with three parameters. It was found that the round samples had the maximum Weibull modulus, indicating the best repeatability. The machined samples exhibited the second best of Weibull modulus. Among the square samples, the 2 mm and 5 mm thick samples had the lowest and the highest Weibull modulus respectively, indicating that the repeatability for the castings was influenced by the wall thickness. The microstructural uniformity and porosity levels are critical factors in determining the repeatability of the high pressure die-castings. A less segregation in the microstructure could uniform the stress distribution in the die-castings and a less porosity in the casting could reduce the sources for brittle fracture. These improved the repeatability in casting production.The authors acknowledge the Engineering and Physical Sciences Research Council (EPSRC), Technology Strategy Board (TSB) and Jaguar Land Rover (JLR) in United Kingdom for financial support

Application of Consensus Scoring and Principal Component Analysis for Virtual Screening against β-Secretase (BACE-1)

BACKGROUND: In order to identify novel chemical classes of β-secretase (BACE-1) inhibitors, an alternative scoring protocol, Principal Component Analysis (PCA), was proposed to summarize most of the information from the original scoring functions and re-rank the results from the virtual screening against BACE-1. METHOD: Given a training set (50 BACE-1 inhibitors and 9950 inactive diverse compounds), three rank-based virtual screening methods, individual scoring, conventional consensus scoring and PCA, were judged by the hit number in the top 1% of the ranked list. The docking poses were generated by Surflex, five scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, and PMF_Score) were used for pose extraction. For each pose group, twelve scoring functions (Surflex_Score, D_Score, G_Score, ChemScore, PMF_Score, LigScore1, LigScore2, PLP1, PLP2, jain, Ludi_1, and Ludi_2) were used for the pose rank. For a test set, 113,228 chemical compounds (Sigma-Aldrich® corporate chemical directory) were docked by Surflex, then ranked by the same three ranking methods motioned above to select the potential active compounds for experimental test. RESULTS: For the training set, the PCA approach yielded consistently superior rankings compared to conventional consensus scoring and single scoring. For the test set, the top 20 compounds according to conventional consensus scoring were experimentally tested, no inhibitor was found. Then, we relied on PCA scoring protocol to test another different top 20 compounds and two low micromolar inhibitors (S450588 and 276065) were emerged through the BACE-1 fluorescence resonance energy transfer (FRET) assay. CONCLUSION: The PCA method extends the conventional consensus scoring in a quantitative statistical manner and would appear to have considerable potential for chemical screening applications

Improvement of Oxidation Resistance of Mild Steel by SiO₂-Al₂O₃ Sol Gel Coating

SiO₂-Al₂O₃ sol gel coating solution was used for coating of mild steel substrate by dip coating technique with withdrawing speeds of 250, 500, 750 and 1000 mm/min. The coatings were subsequently heat treated at 200°C for 1 hour in order to improve their corrosion resistance properties. The coating sol was synthesised using Glycidoxypropyltrimethoxysilane (C₉H₂₀O₅Si) and Aluminium triisopropylate (C₉H₂₁O₃Al). The corrosion resistance of the both coated and uncoated samples was evaluated by the Tafel polarization in NaCl solution. Fourier transformed infrared (FTIR) and energy dispersive spectroscopy (EDS) analyses were used to identify the presence of various functional groups in the coating solution. A comparison of the corrosion resistance of the coated and uncoated mild steel is presented. Variation of corrosion potential $(E_\text{corr})$ has increased and corrosion current density (i_{corr}) has decreased in the coated samples. i_{corr} values of coated specimens, heat treated at 200°C, were 12 to 14 times smaller than those of uncoated specimen. The measured electrochemical parameters indicate that the corrosion resistance was improved by the coating

Creating a modern quality control system for the production of classical men's suits

Considering classic men's suits needed for business life in terms of production, it is seen that it requires specialized production and supervision process. Yet a classical man suit is processed 250 different units within the whole production line until coming to the final version. The main context of this study consists of determination and the analysis of quality features of processing stages, planning of enhancement criteria to be offered based on results and providing the most accurate quality system support to be used in order to perform high quality, fast, cost effective production in our today's production market where competition conditions are most aggravated and improving suggestions for the production of classic men's suits. This research mainly aims to propose a method for determining operations that cause defects and choke flow of production, incurring loss of time and labor and thus costs as well as bottlenecks in the production line of classical men's suit production and enable inspection of these systematically through a control system

Influence of Cu Addition and Austempering Treatment on Mechanical Properties and Microstructure of GGG 50

An investigation was carried out to examine the effect of austempering on the microstructure and mechanical properties of nodular cast iron GGG 50 (DIN EN 1563) alloyed with different amount of copper. Optical, scanning electron microscopy and energy dispersive spectroscopy analyses were performed for microstructural characterization. In addition, hardness and tensile tests were carried out for mechanical properties determination. Specimens were austenitized at 900 degrees C for an hour, then austempered for an hour at 330 degrees C in salt bath and cooled at a room temperature in air. The results indicated that the addition of Cu to GGG 50 encouraged pearlite formation in the matrix structure. In addition, with the austempering heat treatment, the structure was transformed from ferrite + pearlite into ausferrite and retain austenite. Furthermore, for the alloy with 2 wt% Cu addition, it was noted that the graphite nodules diverged from sphericity and Cu was concentrated around the graphite. After austempering, mechanical properties were significantly improved and the highest mechanical properties were found at 1.5 wt% Cu

Glass strengthening by SiO2-TiO2 organically modified silica coating

An alcohol based and water based coating solutions containing SiO2-TiO2 were prepared using sol-gel method. Vickers indented soda-lime-silica float glass samples were coated by applying dip-coating technique and their strengths were determined using Ring-on-Ring test method. Weibull statistics were utilized to examine and interpret the strength results. Clear and transparent coatings on the glasses were obtained. Scanning Electron Microscopy examination revealed that the coatings (alcohol and water based) had a thickness of about 2 gm and partially filled surface cracks. The increase in glass strength of about 170% was obtained with both coating systems. Vickers hardness values of the glasses coated with alcohol based and water based coatings were determined as 3.6 and 4.8 GPa, respectively. In addition, scratch tests performed on the coated glasses indicated that there was a good bonding between the glass samples and the coatings. Fourier Transform Infrared Spectra clearly revealed that the organic groups, Si-O-Ti and Si-O-Si bonds form in the gels heat-treated at 200 degrees C. (c) 2006 Elsevier B.V. All rights reserved

Hydrophobic (water repellant) silica films having high heat resistance by sol-gel dip coating

Water repellant glasses fabricated by coating a water repellant film maintaining the original optical property of the glass have wide variaty of applications. Sol-gel method is widely used to produce films on glasses. High heat resistance and high temperature stabilities of these water repellant films were desirable in many applications