Network approach for capturing ligand-induced subtle global changes in protein structures

Ligand-induced conformational changes in proteins are of immense functional relevance. It is a major challenge to elucidate the network of amino acids that are responsible for the percolation of ligand-induced conformational changes to distal regions in the protein from a global perspective. Functionally important subtle conformational changes (at the level of side-chain noncovalent interactions) upon ligand binding or as a result of environmental variations are also elusive in conventional studies such as those using root-mean-square deviations (r.m.s.d.s). In this article, the network representation of protein structures and their analyses provides an efficient tool to capture these variations (both drastic and subtle) in atomistic detail in a global milieu. A generalized graph theoretical metric, using network parameters such as cliques and/or communities, is used to determine similarities or differences between structures in a rigorous manner. The ligand-induced global rewiring in the protein structures is also quantified in terms of network parameters. Thus, a judicious use of graph theory in the context of protein structures can provide meaningful insights into global structural reorganizations upon perturbation and can also be helpful for rigorous structural comparison. Data sets for the present study include high-resolution crystal structures of serine proteases from the S1A family and are probed to quantify the ligand-induced subtle structural variations.

Theoretical Analysis of the Electromotive Force of a Cell Incorporating a Composition Gradient Solid Electrolyte

New composition gradient solid electrolytes have been designed for application in high temperature solid-state galvanic sensors and in thermodynamic measurements. The functionally gradient electrolyte consists of a solid solution between two or more ionic conductors with a common ion and gradual variation in composition of the other ionic species. Unequal rates of migration of the ions, caused by the presence of the concentration gradient, may result in the development of space charge, manifesting as diffusion potential. Presented is a theoretical analysis of the EMF of cells incorporating gradient solid electrolytes. An analytical expression is derived for diffusion potential, using the thermodynamics of irreversible processes, for different types of concentration gradients and boundary conditions at the electrode/electrolyte interfaces. The diffusion potential of an isothermal cell incorporating these gradient electrolytes becomes negligible if there is only one mobile ion and the transport numbers of the relatively immobile polyionic species and electrons approach zero. The analysis of the EMF of a nonisothermal cell incorporating a composition gradient solid electrolyte indicates that the cell EMF can be expressed in terms of the thermodynamic parameters at the electrodes and the Seebeck coefficient of the gradient electrolyte under standard conditions when the transport number of one of the ions approaches unity.

Examining the effects of species richness on community stability: an assembly model approach

We build dynamic models of community assembly by starting with one species in our model ecosystem and adding colonists. We find that the number of species present first increases, then fluctuates about some level. We ask: how large are these fluctuations and how can we characterize them statistically? As in Robert May's work, communities with weaker interspecific interactions permit a greater number of species to coexist on average. We find that as this average increases, however, the relative variation in the number of species and return times to mean community levels decreases. In addition, the relative frequency of large extinction events to small extinction events decreases as mean community size increases. While the model reproduces several of May's results, it also provides theoretical support for Charles Elton's idea that diverse communities such as those found in the tropics should be less variable than depauperate communities such as those found in arctic or agricultural settings.

A resource based game theoretical model for military conflicts

A resource interaction based game theoretical model for military conflicts is presented in this paper. The model includes both the spatial decision capability of adversaries (decision regarding movement and subsequent distribution of resources) as well as their temporal decision capability (decision regarding level of allocation of resources for conflict with adversary’s resources). Attrition is decided at present by simple deterministic models. An additional feature of this model is the inclusion of the possibility of a given resource interacting with several resources of the adversary.The decisions of the adversaries is determined by solving for the equilibrium Nash strategies given that the objectives of the adversaries may not be in direct conflict. Examples are given to show the applicability of these models and solution concepts.

Estimation of Series Capacitance of a Transformer Winding Based on Frequency-Response Data: An Indirect Measurement Approach

A novel procedure to determine the series capacitance of a transformer winding, based on frequency-response measurements, is reported. It is based on converting the measured driving-point impedance magnitude response into a rational function and thereafter exploiting the ratio of a specific coefficient in the numerator and denominator polynomial, which leads to the direct estimation of series capacitance. The theoretical formulations are derived for a mutually coupled ladder-network model, followed by sample calculations. The results obtained are accurate and its feasibility is demonstrated by experiments on model-coil and on actual, single, isolated transformer windings (layered, continuous disc, and interleaved disc). The authors believe that the proposed method is the closest one can get to indirectly measuring series capacitance.

Deorphanization of Malonyl CoA:ACP Transacylase Drug Target in Plasmodium falciparum (PfFabD) Using Bacterial Antagonists: A Piggyback' Approach for Antimalarial Drug Discovery

Quest for new drug targets in Plasmodium sp. has underscored malonyl CoA:ACP transacylase (PfFabD) of fatty acid biosynthetic pathway in apicoplast. In this study, a piggyback approach was employed for the receptor deorphanization using inhibitors of bacterial FabD enzymes. Due to the lack of crystal structure, theoretical model was constructed using the structural details of homologous enzymes. Sequence and structure analysis has localized the presence of two conserved pentapeptide motifs: GQGXG and GXSXG and five key invariant residues viz., Gln109, Ser193, Arg218, His305 and Gln354 characteristic of FabD enzyme. Active site mapping of PfFabD using substrate molecules has disclosed the spatial arrangement of key residues in the cavity. As structurally similar molecules exhibit similar biological activities, signature pharmacophore fingerprints of FabD antagonists were generated using 0D-3D descriptors for molecular similarity-based cluster analysis and to correlate with their binding profiles. It was observed that antagonists showing good geometrical fitness score were grouped in cluster-1, whereas those exhibiting high binding affinities in cluster-2. This study proves important to shed light on the active site environment to reveal the hotspot for binding with higher affinity and to narrow down the virtual screening process by searching for close neighbors of the active compounds.

Interaction Signatures Stabilizing the NAD(P)-Binding Rossmann Fold: A Structure Network Approach

The fidelity of the folding pathways being encoded in the amino acid sequence is met with challenge in instances where proteins with no sequence homology, performing different functions and no apparent evolutionary linkage, adopt a similar fold. The problem stated otherwise is that a limited fold space is available to a repertoire of diverse sequences. The key question is what factors lead to the formation of a fold from diverse sequences. Here, with the NAD(P)-binding Rossmann fold domains as a case study and using the concepts of network theory, we have unveiled the consensus structural features that drive the formation of this fold. We have proposed a graph theoretic formalism to capture the structural details in terms of the conserved atomic interactions in global milieu, and hence extract the essential topological features from diverse sequences. A unified mathematical representation of the different structures together with a judicious concoction of several network parameters enabled us to probe into the structural features driving the adoption of the NAD(P)-binding Rossmann fold. The atomic interactions at key positions seem to be better conserved in proteins, as compared to the residues participating in these interactions. We propose a ``spatial motif'' and several ``fold specific hot spots'' that form the signature structural blueprints of the NAD(P)-binding Rossmann fold domain. Excellent agreement of our data with previous experimental and theoretical studies validates the robustness and validity of the approach. Additionally, comparison of our results with statistical coupling analysis (SCA) provides further support. The methodology proposed here is general and can be applied to similar problems of interest.

A new approach for understanding ion transport in glasses; example of complex alkali diborate glasses containing lead, bismuth and tellurium oxides

Mechanism of ion transport in glasses continues to be incompletely understood. Several of the theoretical models in vogue fail to rationalize conductivity behaviour when d.c. and a.c. measurements are considered together. While they seem to involve the presence of at least two components in d.c. activation energy, experiments fail to reveal that feature. Further, only minor importance is given to the influence of structure of the glass on the ionic conductivity behaviour. In this paper, we have examined several general aspects of ion transport taking the example of ionically conducting glasses in pseudo binary, yNa(2)B(4)O(7)center dot(1-y) M (a) O (b) (with y = 0 center dot 25-0 center dot 79 and M (a) O (b) = PbO, TeO2 and Bi2O3) system of glasses which have also been recently characterized. Ion transport in them has been studied in detail. We have proposed that non-bridging oxygen (NBO) participation is crucial to the understanding of the observed conductivity behaviour. NBO-BO switching is projected as the first important step in ion transport and alkali ion jump is a subsequent event with a characteristically lower barrier which is, therefore, not observed in any study. All important observations in d.c. and a.c. transport in glasses are found consistent with this model.

Experimental analysis of composite single-lap joints using digital image correlation and comparison with theoretical models

The demand for energy efficient, low weight structures has boosted the use of composite structures assembled using increased quantities of structural adhesives. Bonded structures may be subjected to severe working environments such as high temperature and moisture due to which the adhesive gets degraded over a period of time. This reduces the strength of a joint and leads to premature failure. Measurement of strains in the adhesive bondline at any point of time during service may be beneficial as an assessment can be made on the integrity of a joint and necessary preventive actions may be taken before failure. This paper presents an experimental approach of measuring peel and shear strains in the adhesive bondline of composite single-lap joints using digital image correlation. Different sets of composite adhesive joints with varied bond quality were prepared and subjected to tensile load during which digital images were taken and processed using digital image correlation software. The measured peel strain at the joint edge showed a rapid increase with the initiation of a crack till failure of the joint. The measured strains were used to compute the corresponding stresses assuming a plane strain condition and the results were compared with stresses predicted using theoretical models, namely linear and nonlinear adhesive beam models. A similar trend in stress distribution was observed. Further comparison of peel and shear strains also exhibited similar trend for both healthy and degraded joints. Maximum peel stress failure criterion was used to predict the failure load of a composite adhesive joint and a comparison was made between predicted and actual failure loads. The predicted failure loads from theoretical models were found to be higher than the actual failure load for all the joints.

A Committee Machine Approach for Compressed Sensing Signal Reconstruction

Although many sparse recovery algorithms have been proposed recently in compressed sensing (CS), it is well known that the performance of any sparse recovery algorithm depends on many parameters like dimension of the sparse signal, level of sparsity, and measurement noise power. It has been observed that a satisfactory performance of the sparse recovery algorithms requires a minimum number of measurements. This minimum number is different for different algorithms. In many applications, the number of measurements is unlikely to meet this requirement and any scheme to improve performance with fewer measurements is of significant interest in CS. Empirically, it has also been observed that the performance of the sparse recovery algorithms also depends on the underlying statistical distribution of the nonzero elements of the signal, which may not be known a priori in practice. Interestingly, it can be observed that the performance degradation of the sparse recovery algorithms in these cases does not always imply a complete failure. In this paper, we study this scenario and show that by fusing the estimates of multiple sparse recovery algorithms, which work with different principles, we can improve the sparse signal recovery. We present the theoretical analysis to derive sufficient conditions for performance improvement of the proposed schemes. We demonstrate the advantage of the proposed methods through numerical simulations for both synthetic and real signals.

AN APPROACH FOR EVALUATION OF USE OF GEOCELLS IN FLEXIBLE PAVEMENTS

The design methodology for flexible pavements needs to address the mechanisms of pavement failure, loading intensities and also develop suitable approaches for evaluation of pavement performance. In the recent years, the use of geocells to improve pavement performance has been receiving considerable attention. This paper studies the influence of geocells on the required thickness of pavements by placing it below the granular layers (base and sub-base) and above the subgrade. The reduction in thickness here refers to the reduction in the thickness of the GSB (Granular Sub-base) layer, with a possibility of altogether getting rid of it. To facilitate the analysis, a simple linear elastic approach is used, considering six of the sections as given in the Indian Roads Congress (IRC) code. All the analysis was done using the pavement analysis package KENPAVE. The results show that the use of geocells enables a reduction in pavement thickness.

Estimation of the 2.0(5) helix type i -> i hydrogen bond energy at Aib*-Oxa motif: an isodesmic approach

Bending at the valence angle N-C-alpha-C' (tau) is a known control feature for attenuating the stability of the rare intramolecular hydrogen bonded pseudo five-membered ring C-5 structures, the so called 2.0(5) helices, at Aib. The competitive 3(10)-helical structures still predominate over the C5 structures at Aib for most values of tau. However at Aib*, a mimic of Aib where the carbonyl 0 of Aib is replaced with an imidate N (in 5,6-dihydro-4H-1,3-oxazine = Oxa), in the peptidomimic Piv-Pro-Aib*-Oxa (1), the C(5)i structure is persistent in both crystals and in solution. Here we show that the i -> i hydrogen bond energy is a more determinant control for the relative stability of the C5 structure and estimate its value to be 18.5 +/- 0.7 kJ/mol at Aib* in 1, through the computational isodesmic reaction approach, using two independent sets of theoretical isodesmic reactions. (C) 2014 Elsevier Ltd. All rights reserved.

Modulation of Electronic and Self-Assembly Properties of a Donor-Acceptor-Donor-Based Molecular Materials via Atomistic Approach

The performance of molecular materials in optoelectronic devices critically depends upon their electronic properties and solid-state structure. In this report, we have synthesized sulfur and selenium based (T4BT and T4BSe) donor-acceptor-donor (D-A-D) organic derivatives in order to understand the structure-property correlation in organic semiconductors by selectively tuning the chalcogen atom. The photophysical properties exhibit a significant alteration upon varying a single atom in the molecular structure. A joint theoretical and experimental investigation suggests that replacing sulfur with selenium significantly reduces the band gap and molar absorption coefficient because of lower electronegativity and ionization potential of selenium. Single-crystal X-ray diffraction analysis showed differences in their solid-state packing and intermolecular interactions. Subsequently, difference in the solid-state packing results variation in self-assembly. Micorstructural changes within these materials are correlated to their electrical resistance variation, investigated by conducting probe atomic force microscopy (CP-AFM) measurements. These results provide useful guidelines to understand the fundamental properties of D-A-D materials prepared by atomistic modulation.

Intramolecular hydrogen bonds involving organic fluorine in the derivatives of hydrazides: an NMR investigation substantiated by DFT based theoretical calculations

The rare examples of intramolecular hydrogen bonds (HB) of the type the N-H center dot center dot center dot F-C, detected in a low polarity solvent in the derivatives of hydrazides, by utilizing one and two-dimensional solution state multinuclear NMR techniques, are reported. The observation of through-space couplings, such as, (1h)J(FH), and (1h)J(FN), provides direct evidence for the existence of intra-molecular HB. Solvent induced perturbations and the variable temperature NMR experiments unambiguously establish the presence of intramolecular HB. The existence of multiple conformers in some of the investigated molecules is also revealed by two dimensional HOESY and N-15-H-1 HSQC experiments. The H-1 DOSY experimental results discard any possibility of self or cross dimerization of the molecules. The derived NMR experimental results are further substantiated by Density Function Theory (DFT) based Non Covalent Interaction (NCI), and Quantum Theory of Atom in Molecule (QTAIM) calculations. The NCI calculations served as a very sensitive tool for detection of non-covalent interactions and also confirm the presence of bifurcated HBs.

Capability approach-based evaluation of a biomass cook-stove design

What is the scope and responsibilities of design? This work partially answers this by employing a normative approach to design of a biomass cook stove. This study debates on the sufficiency of existing design methodologies in the light of a capability approach. A case study of a biomass cook stove Astra Ole has elaborated the theoretical constructs of capability approach, which, in turn, has structured insights from field to evaluate the product. Capability approach based methodology is also prescriptively used to design the mould for rapid dissemination of the Astra Ole.