Distilling the essential features of a protein surface for improving protein-ligand docking,scoring, and virtual screening

For the successful identification and docking of new ligands to a protein target by virtual screening, the essential features of the protein and ligand surfaces must be captured and distilled in an efficient representation. Since the running time for docking increases exponentially with the number of points representing the protein and each ligand candidate, it is important to place these points where the best interactions can be made between the protein and the ligand. This definition of favorable points of interaction can also guide protein structure-based ligand design, which typically focuses on which chemical groups provide the most energetically favorable contacts. In this paper, we present an alternative method of protein template and ligand interaction point design that identifies the most favorable points for making hydrophobic and hydrogen–bond interactions by using a knowledge base. The knowledge-based protein and ligand representations have been incorporated in version 2.0 of SLIDE and resulted in dockings closer to the crystal structure orientations when screening a set of 57 known thrombin and glutathione S–transferase (GST) ligands against the apo structures of these proteins. There was also improved scoring enrichment of the dockings, meaning better differentiation between the chemically diverse known ligands and a 15,000-molecule dataset of randomly-chosen small organic molecules. This approach for identifying the most important points of interaction between proteins and their ligands can equally well be used in other docking and design techniques. While much recent effort has focused on improving scoring functions for protein-ligand docking, our results indicate that improving the representation of the chemistry of proteins and their ligands is another avenue that can lead to significant improvements in the identification, docking, and scoring of ligands.(These authors contributed equally to this work)     

Synthesis and structure of new Schiff base derivatives obtained from 2-(formylphenyl)mercury bromide

Reactions of (2-formylphenyl)mercury(II) bromide 10 with primary amines give mono-, bis- and tris- Schiff base derivatives (11-18). Structures of the synthesized compounds show the presence of five-membered intramolecular Hg?N interaction. Luminescence studies of the compounds have been performed. Attempts to use the synthesized compounds for binding neutral donor molecules or fluoride ions were unsuccessful.     

Study of optical band gap and carbon cluster sizes formed in 100 MeV Si8+ and 145 MeV Ne6+ ions irradiated polypropylene polymer

A wide variety of material modifications in polymers have been studied by using ion irradiation techniques. Extensive research has focused on to Swift Heavy Ions (MeV’s energy), probably because of good controllability and the large penetration length in polymers. High energy ion irradiation tends to damage polymers significantly by electronic excitation and ionization. It may result into the creation of latent tracks and can also cause formation of radicals such as ablation, sputtering, chain scission and intermolecular cross-linking, creation of triple bonds and unsaturated bonds and loss volatile fragments. Polypropylene polymer films of thickness 50 μm were irradiated to the fluences of 1 × 10¹⁰, 3 × 10¹⁰, 1 × 10¹¹, 3 × 10¹¹, 6 × 10¹¹ and 1 × 10¹² ions/cm² with Si⁸⁺ ions of 100 MeV energy from Pelletron accelerator at Inter University Accelerator Centre (IUAC), New Delhi and Ne⁶⁺ ions of 145 MeV to the fluences of 10⁸, 10¹⁰, 10¹¹, 10¹² and 10¹³ ions/cm³ from Variable Energy Cyclotron Centre, Kolkata. Optical modifications were characterized by UV towards the red end of the spectrum with the increase of the fluence. Value of optical band gap E _g shows a decreasing trend with ion fluence irradiated with both kinds of ions. Cluster size N, the number of carbon atoms per conjugation length increases with increasing ion dose. Cluster size also increases with the increase of electronic stopping power.      

Trumping and Power Majorization

Majorization is a basic concept in matrix theory that has found applications in numerous settings over the past century. Power majorization is a more specialized notion that has been studied in the theory of inequalities. On the other hand, the trumping relation has recently been considered in quantum information, specifically in entanglement theory. We explore the connections between trumping and power majorization. We prove an analogue of Rado’s theorem for power majorization and consider a number of examples.     

Nonlinear quantum cosmology

We study the effects of an information-theoretically motivated nonlinear correction to the Wheeler-deWitt equation in the minisuperspace scheme for flat, k = 0, Friedmann–Robertson–Walker universes. When the only matter is a cosmological constant, the nonlinearity can provide a barrier that screens the original Big Bang, leading to the quantum creation of a universe through tunneling just as in the k = 1 case. When the matter is instead a free massless scalar field, the nonlinearity can again prevent a contracting classical universe from reaching zero size by creating a bounce. Our studies here are self-consistent to leading order in perturbation theory for the nonlinear effects.     

An information-theoretic link between spacetime symmetries and quantum linearity

A nonlinear generalisation of Schrodinger’s equation is obtained using information-theoretic arguments. The nonlinearities are controlled by an intrinsic length scale and involve derivatives to all orders thus making the equation mildly nonlocal. The nonlinear equation is homogeneous, separable, conserves probability, but is not invariant under spacetime symmetries. Spacetime symmetries are recovered when a dimensionless parameter is tuned to vanish, whereby linearity is simultaneously established and the length scale becomes hidden. It is thus suggested that if, in the search for a more basic foundation for Nature’s Laws, an inference principle is given precedence over symmetry requirements, then the symmetries of spacetime and the linearity of quantum theory might both be emergent properties that are intrinsically linked. Supporting arguments are provided for this point of view and some testable phenomenological consequences are highlighted. The generalised Klien-Gordon and Dirac equations are also studied, leading to the suggestion that nonlinear quantum dynamics with intrinsically broken spacetime symmetries might be relevant to understanding the problem of neutrino mass (lessness) and oscillations: among other observations, this approach hints at the existence of a hidden discrete family symmetry in the Standard Model of particle physics.     

Generation of sub wavelength super-long dark channel using high NA lens axicon

We investigate the focusing properties of a double-ring-shaped azimuthally polarized beam by a high numerical aperture (NA) lens axicon based on vector diffraction theory. We observe that our proposed system generates a sub wavelength focal hole of 0.5λ having large uniform focal depth of 48λ without any annular aperture. We also observed that the distribution of the total intensity near the focus has little variation with the degree of truncation β of the incident beam by the pupil. The authors expect such a super-long dark channel may find applications in optical, biological, and atmospheric sciences.     

Numerical scheme with convergence for a generalized time‐fractional Telegraph‐type equation

In this work, we design and analyze a numerical scheme for solving the generalized time‐fractional Telegraph‐type equation (GTFTTE) which is defined using the generalized time fractional derivative (GTFD) proposed recently by Agrawal. The GTFD involves the scale and the weight functions, and reduces to the traditional Caputo derivative for a particular choice of the weight and the scale functions. The scale and the weight functions play an important role in describing the behavior of real‐life physical systems and thus we study the solution behavior of the GTFTTE by varying the weight and the scale functions in the GTFD. We investigate the solution profile of the GTFTTE under some of these choices. We also provide the stability and the convergence analysis of the proposed numerical scheme for the GTFTTE. We consider two test examples to perform numerical simulations.     

Electrochemical impedance spectroscopic studies on aging-dependent electrochemical degradation of p-toluene sulfonic acid-doped polypyrrole thin film

The conducting polymer polypyrrole thin film was galvanostatically polymerized on stainless steel substrate for the supercapacitor electrode. The electrochemical stability of the electrode was monitored each 30 days of aging up to 90 days. The FTIR analysis showed an increase in intensity of the absorption peaks, especially high growth of the carbonyl peaks after 90 days of aging. The electrochemical capacitance degradation of the electrode was studied using cyclic voltammetric and galvanostatic charge/discharge analysis in 1 M Na₂SO₄ electrolyte, which showed ~?53% of fading in the initial specific capacitance value after 90 days. Further, the electrochemical degradation of polypyrrole electrodes was analyzed in detail using electrochemical impedance spectroscopy. The analysis showed a large increase in the internal resistance and low-power deliverability of the electrode with respect to aging as the main reasons for the degradation of specific capacitance of the polypyrrole electrode.