BindingDB in 2015: A public database for medicinal chemistry, computational chemistry and systems pharmacology.

BindingDB, www.bindingdb.org, is a publicly accessible database of experimental protein-small molecule interaction data. Its collection of over a million data entries derives primarily from scientific articles and, increasingly, US patents. BindingDB provides many ways to browse and search for data of interest, including an advanced search tool, which can cross searches of multiple query types, including text, chemical structure, protein sequence and numerical affinities. The PDB and PubMed provide links to data in BindingDB, and vice versa; and BindingDB provides links to pathway information, the ZINC catalog of available compounds, and other resources. The BindingDB website offers specialized tools that take advantage of its large data collection, including ones to generate hypotheses for the protein targets bound by a bioactive compound, and for the compounds bound by a new protein of known sequence; and virtual compound screening by maximal chemical similarity, binary kernel discrimination, and support vector machine methods. Specialized data sets are also available, such as binding data for hundreds of congeneric series of ligands, drawn from BindingDB and organized for use in validating drug design methods. BindingDB offers several forms of programmatic access, and comes with extensive background material and documentation. Here, we provide the first update of BindingDB since 2007, focusing on new and unique features and highlighting directions of importance to the field as a whole

BindingDB: a web-accessible database of experimentally determined protein–ligand binding affinities

BindingDB () is a publicly accessible database currently containing ∼20 000 experimentally determined binding affinities of protein–ligand complexes, for 110 protein targets including isoforms and mutational variants, and ∼11 000 small molecule ligands. The data are extracted from the scientific literature, data collection focusing on proteins that are drug-targets or candidate drug-targets and for which structural data are present in the Protein Data Bank. The BindingDB website supports a range of query types, including searches by chemical structure, substructure and similarity; protein sequence; ligand and protein names; affinity ranges and molecular weight. Data sets generated by BindingDB queries can be downloaded in the form of annotated SDfiles for further analysis, or used as the basis for virtual screening of a compound database uploaded by the user. The data in BindingDB are linked both to structural data in the PDB via PDB IDs and chemical and sequence searches, and to the literature in PubMed via PubMed IDs

Experimental and DFT Studies: Novel Structural Modifications Greatly Enhance the Solvent Sensitivity of Live Cell Imaging Dyes

Structural modifications of previously reported merocyanine dyes (J. Am. Chem. Soc. 2003, 125, 4132–4145) were found to greatly enhance the solvent dependence of their absorbance and fluorescence emission maxima. Density functional theory (DFT) calculations have been performed to understand the differences in optical properties between the new and previously synthesized dyes. Absorption and emission energies were calculated for several new dyes using DFT vertical self-consistent reaction field methods (VSCRF). Geometries of ground and excited states were optimized with a Conductor-like screening model (COSMO) and self-consistent-field (SCF) methods. The new dyes have enhanced zwitterionic character in the ground state, and much lower polarity in the excited state, as shown by the DFT-VSCRF calculations. Consistently, the position of the absorption bands are strongly blue-shifted in more polar solvent (methanol compared to benzene) as predicted by the DFT spectral calculations. Inclusion of explicit H-bonding solvent molecules within the quantum model further enhances the predicted shifts, and is consistent with the observed spectral broadening. Smaller, but significant spectral shifts in polar versus nonpolar solvent are predicted and observed for emission bands. The new dyes show large fluorescence quantum yields in polar hydrogen bonding solvents; qualitatively, the longest bonds along the conjugated chain at the excited S1 state minimum are shorter in the more polar solvent, inhibiting photoisomerization. The loss of photostability of the dyes is a consequence of the reaction with and electron transfer to singlet oxygen, starting oxidative dye cleavage. The calculated vertical ionization potentials of three dyes I-SO, AI-SO(4), and AI-BA(4) in benzene and methanol are consistent with their relative photobleaching rates; the charge distributions along the conjugated chains for the three dyes are similarly predictive of higher reaction rates for AI-SO(4) and AI-BA(4) than for I-SO. Time dependent DFT (TDDFT) calculations were also performed on AI-BA(4); these were less accurate than the VSCRF method in predicting the absorption energy shift from benzene (C6H6) to methanol (MeOH)

BindingDB: a web-accessible database of

experimentally determined protein–ligand binding affinitie

Analysis of the laterally bent piezoelectric semiconductor fibers with variable cross-sections

Piezoelectric semiconductor materials (PS) have attracted much attention in recent years due to their unique properties. This paper explores the electromechanical coupling behavior of bent piezoelectric semiconductor fibers with non-uniform cross-sectional areas. The study uses the generalized differential quadrature method (GDQM) to numerically solve the field equations with variable coefficients derived from piezoelectric theory. The research examines the mechanical and electrical field distribution of bent variable cross-section fibers, comparing the performances of nonuniform fibers with different profiles. The study reveals that the variable cross-section profile of the fiber changes the characteristic of the uniform fiber’s electrical distribution along the axis, and it exhibits a more sensitive and stronger electrical response to the same external force. The research also shows that the concavity and convexity of the radius distribution function of the non-uniform fibers determine whether there are extreme points of surface potential. Finally, the study suggests that by designing extreme points of the PS fiber profile, surface potential extreme points can be artificially created at the same location. These results offer a theoretical direction for creating advanced piezoelectric semiconductor nanodevices and present novel insights into designing higher-efficiency nanogenerators and mechanical strain sensors in the future