Shashank Shekhar

Sanjeevini: a freely accessible web-server for target directed lead molecule discovery

BackgroundComputational methods utilizing the structural and functional information help to understand specific molecular recognition events between the target biomolecule and candidate hits and make it possible to design improved lead molecules for the target.ResultsSanjeevini represents a massive on-going scientific endeavor to provide to the user, a freely accessible state of the art software suite for protein and DNA targeted lead molecule discovery. It builds in several features, including automated detection of active sites, scanning against a million compound library for identifying hit molecules, all atom based docking and scoring and various other utilities to design molecules with desired affinity and specificity against biomolecular targets. Each of the modules is thoroughly validated on a large dataset of protein/DNA drug targets.ConclusionsThe article presents Sanjeevini, a freely accessible user friendly web-server, to aid in drug discovery. It is implemented on a tera flop cluster and made accessible via a web-interface at http://www.scfbio-iitd.res.in/sanjeevini/sanjeevini.jsp. A brief description of various modules, their scientific basis, validation, and how to use the server to develop in silico suggestions of lead molecules is provided.

Effect of Severe Plastic Deformation in Machining Elucidated via Rate-Strain-Microstructure Mappings

Machining induces severe plastic deformation (SPD) in the chip and on the surface to stimulate dramatic microstructural transformations which can often result in a manufactured component with a fine-grained surface. The aim of this paper is to study the one-to-one mappings between the thermomechanics of deformation during chip formation and an array of resulting microstructural characteristics in terms of central deformation parameters–strain, strain-rate, temperature, and the corresponding Zener–Hollomon (ZH) parameter. Here, we propose a generalizable rate-strain-microstructure (RSM) framework for relating the deformation parameters to the resulting deformed grain size and interface characteristics. We utilize Oxley’s model to calculate the strain and strain-rate for a given orthogonal machining condition which was also validated using digital imaging correlation-based deformation field characterization. Complementary infrared thermography in combination with a modified-Oxley’s analysis was utilized to characterize the temperature in the deformation zone where the SPD at high strain-rates is imposed. These characterizations were utilized to delineate a suitable RSM phase-space composed of the strain as one axis and the ZH parameter as the other. Distinctive one-to-one mappings of various microstructures corresponding to an array of grain sizes and grain boundary distributions onto unique subspaces of this RSM space are shown. Building on the realization that the microstructure on machined surfaces is closely related to the chip microstructure derived from the primary deformation zone, this elucidation is expected to offer a reliable approach for controlling surface microstructures from orthogonal machining.

Bhageerath-H: A homology/ab initio hybrid server for predicting tertiary structures of monomeric soluble proteins

BackgroundThe advent of human genome sequencing project has led to a spurt in the number of protein sequences in the databanks. Success of structure based drug discovery severely hinges on the availability of structures. Despite significant progresses in the area of experimental protein structure determination, the sequence-structure gap is continually widening. Data driven homology based computational methods have proved successful in predicting tertiary structures for sequences sharing medium to high sequence similarities. With dwindling similarities of query sequences, advanced homology/ ab initio hybrid approaches are being explored to solve structure prediction problem. Here we describe Bhageerath-H, a homology/ ab initio hybrid software/server for predicting protein tertiary structures with advancing drug design attempts as one of the goals.ResultsBhageerath-H web-server was validated on 75 CASP10 targets which showed TM-scores ≥0.5 in 91% of the cases and Cα RMSDs ≤5Å from the native in 58% of the targets, which is well above the CASP10 water mark. Comparison with some leading servers demonstrated the uniqueness of the hybrid methodology in effectively sampling conformational space, scoring best decoys and refining low resolution models to high and medium resolution.ConclusionBhageerath-H methodology is web enabled for the scientific community as a freely accessible web server. The methodology is fielded in the on-going CASP11 experiment.

Statistical characterization of nanostructured materials from severe plastic deformation in machining

Endowing conventional microcrystalline materials with nanometer-scale grains at the surfaces can offer enhanced mechanical properties, including improved wear, fatigue, and friction properties, while simultaneously enabling useful functionalizations with regard to biocompatibility, osseointegration, electrochemical performance, etc. To inherit such multifunctional properties from the surface nanograined state, existing approaches often use coatings that are created through an array of secondary processing techniques (e.g., physical or chemical vapor deposition, surface mechanical attrition treatment, etc.). Obviating the need for such surface processing, recent empirical evidence has demonstrated the introduction of integral surface nanograin structures on bulk materials as a result of severe plastic deformation during machining-based processes. Building on these observations, if empirically driven, process–structure mappings can be developed, it may be possible to engineer enhanced nanoscale surface microstructures directly using machining processes while simultaneously incorporating them within existing computer-numeric-controlled manufacturing systems. Toward this end, this article provides a statistical characterization of nanograined metals created by severe plastic deformation in machining-based processes that maps machining conditions to the resulting microstructure, namely, the mean grain size. A specialized designed experiments approach is used to hypothesize and test a linear mixed-effects model of two important machining parameters. Unlike standard analysis approaches, the statistical dependence between subsets of experimental grain size observations is accounted for and it is shown that ignoring this inherent dependence can yield misleading results for the mean response function. The statistical model is applied to pure copper specimens to identify the factors that most significantly contribute to variability in the mean grain size and is shown to accurately predict the mean grain size under a few scenarios.

Cut-off deviation for CSL boundaries in recrystallized face-centered cubic materials

Abstract Brandon’s criterion is frequently used to quantify distribution of coincident site lattice (CSL) boundaries in studies related to grain boundary character distribution. This criterion is based on theoretical considerations and is meant to define a range within which special boundaries may exist. Experiments have repeatedly shown that this range includes boundaries which do not show special properties. A broad aim of this study is to explore if there exists a cut-off in deviation which includes only boundaries with special properties. While most other criteria in literature are based on theoretical dependence of secondary dislocation spacing, in this work we find the cut-off deviation through experimental data of recrystallised microstructures from in situ as well as ex-situ heating experiments. Deviation from structure was considered in terms of both, deviation of misorientation axis-angle as well as deviation of the boundary plane from the symmetric tilt orientation. Our results indicate that the deviation in terms of misorientation angle is more important than boundary plane deviation. We also show that the limiting deviation for various orders of twin boundaries (Σ3n) in a recrystallized microstructure is a constant and approximately 1° which is significantly lower than that defined by Brandon’s criterion. We show that this constant cut-off deviation for various Σ3n CSL boundaries can also be obtained by assuming that the secondary dislocations are spaced proportional to displacement shift complete lattice vector. Similar analysis was also carried out for non-Σ3n boundaries but due to limited statistics, no cut-off value could be deduced for these boundaries.

User-independent EBSD parameters to study the progress of recovery and recrystallization in Cu-Zn alloy during in situ heating.

Microstructural evolution of cold‐rolled Cu–5%Zn alloy during in situ heating inside field‐emission scanning electron microscope was utilized to obtain user‐independent parameters in order to trace the progress of static recovery and recrystallization. Electron back‐scattered diffraction (EBSD)‐based orientation imaging microscopy was used to obtain micrographs at various stages of in situ heating. It is shown that unlike the pre‐existing methods, additional EBSD‐based parameter can be used to trace the progress of recovery and recrystallization, which is not dependent on user input and hence less prone to error. True strain of 0.3 was imposed during cold rolling of alloy sample. Rolled sample was subjected to in situ heating from room temperature to 500°C (∼0.58 Tm) with soaking time of 10 min, at each of the intermediate temperatures viz. 100, 200, 300, 400 and 450°C. After reaching 500°C, the sample was kept at this temperature for a maximum duration of around 15 h. The sample showed clear signs of recovery for temperature up to 450°C, and at 500°C, recrystallization started to take place. Recrystallization kinetics was moderate, and full recrystallization was achieved in approximately 120 min.

Effect of Machining Configurations on the Electrochemical Response of Mild Steel in 3.5% NaCl Solution

The present work is based on the study of the electrochemical response of mild steel as a function of machining configurations. The variable parameters were rake angle and turning speed, while feed rate and depth of cut remained fixed. Dynamic polarization tests and electrochemical impedance spectroscopy in 3.5% NaCl solution were done to analyze the electrochemical behavior of mild steels with the variation of rake angle and turning speed. The electrochemical response showed that the steel machined at higher speed and positive rake angle had higher resistance to charge transfer. Similarly, steel machined at lower speed and negative rake angle showed lower resistance to charge transfer. The results obtained in this study suggest that machining on mild steel should be carried out at positive rake angle and at higher speed to have smoother surface finish, strain-relieved surface grains, and subsequently better corrosion resistance, which was measured from corrosion current as determined by the Tafel extrapolation from the polarization plots.

Post-order based routing & transport protocol for wireless sensor networks☆

Abstract In this paper, we propose a lightweight, application independent transport protocol for communication of the nodes belonging to a wireless sensor network (WSN) with the nodes belonging to a local area network. The framework consists of a novel downstream routing scheme and a well-known tree based upstream routing protocol for WSNs. The downstream routing protocol leverages Post-order Numbering (PN) of sensor nodes in the collection tree network formed and maintained by the upstream routing protocol. Through the proposed transport framework, using a technique similar to NATing, we achieve a seamless integration of WSNs and IP networks. The proposed protocol was not only evaluated by extensive simulations, but also implemented on a real test bed to show its practical deployability. We built our test bed around a small Wireless Distribution System (WDS) consisting of two laptop computers and eight Micaz motes attached with MTS300 sensor boards. We connected one of the computers in WDS via Ethernet to the LAN while the other operated as a server with a serial forwarder. A gateway board was attached to the second computer via a USB port which enabled it to function also as a base station for the WSN. A distinct advantage of the proposed framework is that an IP client can directly communicate with a sensor node through its base station.

Interactive Effects of Strain, Strain-Rate and Temperatures on Microstructure Evolution in High Rate Severe Plastic Deformation

During high rate severe plastic deformation (HRSPD), strain and strain-rate are not the only external factors that determine microstructural transformations in materials, temperature-rise due to heat generation from deformation processes, also plays an important role. Temperature may influence the microstructure directly by controlling grain growth kinetics and it may also have an indirect effect through the interactive effect on material behavior, which in turn, influences strain and strain-rate parameters. This complex thermomechanics of HRSPD can lead to myriad of microstructure and consequently, material properties and phenomenon. These deformation parameters can be utilized as a ‘fingerprint’ for the resulting microstructure, and the properties and phenomenon related to it. Here, we capture some of these microstructural transformations by relating grain and sub-grain sizes, to the deformation parameters. In doing so, we find evidence of continuous dynamic recrystallization operative under these HRSPD conditions, where the interplay of strain, strain rate and temperatures offer varying degrees of multimodality in the grain-size distributions.

Fractal Analysis as Applied to Fractography in Ferritic Stainless Steel

Fractal analysis has been developed as a tool to analyze the fractal characteristics with less sensitivity to magnification over a wide scale, which can also be used to quantify the fractographic data. In this work, two different techniques of fractal analysis were used to calculate the fractal dimension. In the first method, the fracture surface morphology was utilized, and in the second method, the roughness profile of the fracture surface was utilized in order to calculate the fractal dimension. The purpose of the work is to compare the effectiveness of these two fractal techniques in characterizing the mode of fracture. For it, the results of fractal analysis were compared with the quantified results obtained using conventional fractography analysis. Moreover, fractal dimension obtained using roughness profile had a positive linear correspondence with impact energy, and this result has been discussed in terms of fracture micromechanism.