‘All That Glitters Is Not Gold’: High-Resolution Crystal Structures of Ligand-Protein Complexes Need Not Always Represent Confident Binding Poses

Our understanding of the structure–function relationships of biomolecules and thereby applying it to drug discovery programs are substantially dependent on the availability of the structural information of ligand–protein complexes. However, the correct interpretation of the electron density of a small molecule bound to a crystal structure of a macromolecule is not trivial. Our analysis involving quality assessment of ~0.28 million small molecule–protein binding site pairs derived from crystal structures corresponding to ~66,000 PDB entries indicates that the majority (65%) of the pairs might need little (54%) or no (11%) attention. Out of the remaining 35% of pairs that need attention, 11% of the pairs (including structures with high/moderate resolution) pose serious concerns. Unfortunately, most users of crystal structures lack the training to evaluate the quality of a crystal structure against its experimental data and, in general, rely on the resolution as a ‘gold standard’ quality metric. Our work aims to sensitize the non-crystallographers that resolution, which is a global quality metric, need not be an accurate indicator of local structural quality. In this article, we demonstrate the use of several freely available tools that quantify local structural quality and are easy to use from a non-crystallographer’s perspective. We further propose a few solutions for consideration by the scientific community to promote quality research in structural biology and applied areas.     

A genetic algorithm based heat transfer analysis of a bloom re‐heating furnace

A heat transfer model, coupled with an optimization scheme has been presented in designing a re‐heating furnace typically used in the integrated steel plants. Numerical solution of the pertinent differential equations were coupled with the optimal settings of the burner and the velocity of the bloom, using biologically inspired genetic algorithms (GAs) and differential evolution (DE), which led to optimized temperature profiles satisfying bloom dropout temperature constraints. The ease of application and efficiency of solution methodology demonstrated in this paper suggest further application of GAs and DE to more complex engineering design problems.     

Arsenic groundwater contamination and its health effects in the state of Uttar Pradesh (UP) in upper and middle Ganga plain, India: a severe danger

This communication presents results of our 2-year survey on groundwater arsenic contamination in three districts Ballia, Varanasi and Gazipur of Uttar Pradesh (UP) in the upper and middle Ganga plain, India. Analyses of 4,780 tubewell water samples revealed that arsenic concentrations in 46.5% exceeded 10 microg/L, in 26.7%, 50 microg/L and in 10% 300 microg/L limits. Arsenic concentrations up to 3,192 microg//L were observed. The age of tubewells (n=1,881) ranged from less than a year to 32 years, with an average of 6.5 years. Our study shows that older tubewells had a greater chance of contamination. Depth of tubewells (n=3,810) varied from 6 to 60.5 m with a mean of 25.75 m. A detailed study in three administrative units within Ballia district, i.e. block, Gram Panchayet, and village was carried out to assess the magnitude of the contamination. Before our survey the affected villagers were not aware that they were suffering from arsenical toxicity through contaminated drinking water. A preliminary clinical examination in 11 affected villages (10 from Ballia and 1 from Gazipur district) revealed typical arsenical skin lesions ranging from melanosis, keratosis to Bowens (suspected). Out of 989 villagers (691 adults, and 298 children) screened, 137 (19.8%) of the adults and 17 (5.7%) of the children were diagnosed to have typical arsenical skin lesions. Arsenical neuropathy and adverse obstetric outcome were also observed, indicating severity of exposure. The range of arsenic concentrations in hair, nail and urine was 137-10,900, 764-19,700 microg/kg, and 23-4,030 microg/L, respectively. The urine, hair and nail concentrations of arsenic correlated significantly (r=0.76, 0.61, and 0.55, respectively) with drinking water arsenic concentrations. The similarity to previous studies on arsenic contamination in West Bengal, Bihar and Bangladesh indicates that people from a significant part of the surveyed areas in UP are suffering and this will spread unless drives to raise awareness of arsenic toxicity are undertaken and an arsenic safe water supply is immediately introduced.     

Surface integrity study of WEDM with various wire electrodes: experiments and analysis

Abstract

Wire electrical discharge machining (WEDM) is always significant for its high-precision machining. However, due to the generation of high discharge energy during machining, machined surfaces are often got distorted. These might be upgraded by choosing the correct tool with proper machining condition. The effects of the electrode materials and process parameters on different responses of WEDM like average surface roughness, recast layer thickness, and surface morphology are systematically examined here to enhance the knowledge of WEDM and its correlation with electrode property. The experiments have been carried out on one of the expensive steel namely Maraging steel 300 due to its applicability in tooling and aerospace industries. Plain brass wire, zinc-coated brass wire (ZCB), and silver-coated brass (SCB) wires are used as a tool electrode for analysis. Comparative experimental studies prove that among BW, ZCB, and SCB, the overall performance of SCB is commendable owing to the high-quality surface considering control parameters in low discharge energy level. However, the second-best performance is shown by ZCB.     

An analytical and experimental approach for pressure distribution analysis of a particular lobe and plain bearing performance keeping in view of all impeding varying parameters associating with fixed lubrication SAE20W40

This paper presents both analytical and experimental pressure analysis approach of a typical Lobe and plain bearing for determining effective performance of the bearing. This is found to be dependent on several variables viz. angular velocity (1200-1900 rpm), load (300-750 N) and pressure angle (0°-180°). This study in particular has been carried out for better rectifications and comparative prediction of lobe and plain bearing in terms of pressure distribution behavior under lubrication oil grade of SAE20W40. Influencing parameters were varied in this set up only to get optimum parametric combination considering all relevant practical issues. The experimentation was done based on significant directives of relevant literatures in these sectors. Attempt was made to compare the analytical findings with experimental results and found matched appreciably. After that attention was diverted to find the nature of pressure and load carrying capacity at various fluctuating speed and load with a fixed lubrication of SAE20W40 for appropriate decision making towards its characteristic performance. The analytical data generated by MATLAB are compared with experimental data which is generated by JBTR.

     

Development of a mathematical model for multihearth roasters

A simultaneous heat and mass transfer model has been developed for the multiheart roasters, considering dead roasting of chalcopyrite as a typical roasting reaction. Various mass and energy balances have been worked out during the development of this model yielding coupled nonlinear partial differential equations with highly complex boundary conditions. These equations have been solved numerically using a line-by-line finite difference approach to obtain profiles of gas temperature, solid temperature, oxygen concentration, and solid fraction reacted in the roaster. The trend of the computed results appears to be realistic and can be easily explained from simple physical considerations. The effects of gas preheating and the heat transfer coefficient between the solid and the gas upon the roasting process are examined. The results show that gas preheating is beneficial for the roasting process, and the process parameters, such as particle size, gas flow rate,etc., must be adjusted so as to give the desirable value of the heat transfer coefficient needed for proper roasting.     

Re-evaluation of heat transfer effects in carbon gasification reaction

The gasification reaction of carbon (viz. CO₂ + C = 2 CO) plays a very important role in the direct reduction of iron oxides as it may be the rate controlling step for the overall process. It is well established that heat and mass transfer processes affect the kinetics of gasification considerably. During this investigation several inconsistencies were noted in mathematical analysis of simultaneous heat and mass transfer of this process reported in literature. In this paper an attempt has been made to remove the inconsistencies. Appropriate differential equations for the system have been formulated and certain predictions have been compared with the existing values in literature.     

Studies of blood pH and blood gases of humans under moderate and high altitude stress: effect of acetazolamide supplementation

Studies have been carried out on blood pH, Pco2, Po2, (HCO‐3), sodium and potassium levels of 30 human subjects at a moderate and at a high altitude in the north eastern Himalayan range. Blood pH was found to be increased, whereas Po2 and PCo2 levels decreased appreciably under high altitude stress. However, no significant change was observed in plasma bicarbonate level. Plasma sodium level was found to be lowered, while that of potassium level was raised at high altitude in comparison to the moderate altitude. Treatment with acetazolamide was found to be effective in lowering blood pH, Pco2 (HCO‐3) and plasma potassium level at high altitude, while PO2 level increased in comparison to the placebo group. On return of the subjects from high to moderate altitude, the studied parameters reverted to the initial moderate altitude base data.     

Plasma immunoglobulin levels of humans under high altitude stress

Studies have been carried out on plasma IgG, IgA, IgM and IgD levels of 20 male Indian sea level dwellers at sea level and at a high altitude (3658 m). An increase in plasma IgG, IgA and IgD levels with no change in IgM were observed under high altitude stress in comparison to the sea level base data. On return of the subjects from high to sea level, IgA and IgD levels, but not the IgG, reverted to the values observed at the initial sea level conditions.