Drug discovery projects in the pharmaceutical industry accumulate thousands of chemical structures and ten-thousands data points from a dozen or more biological pharmacological assays. A sufficient interpretation requires understanding, which molecular families are present, structural motifs correlate with measured properties, tiny changes cause large property changes. Data visualization analysis software intelligence to support chemists this task is rare. In an attempt contribute filling...

Knowledge about the 3-dimensional structure, orientation and interaction of chemical compounds is important in many areas science technology. X-ray crystallography one experimental techniques capable providing a large amount structural information for given compound, it widely used characterisation organic metal-organic molecules. The method provides precise 3D coordinates atoms inside crystals, however, does not directly deliver certain characteristics such as bond orders, delocalization,...

We present OSIRIS, an entirely in-house developed drug discovery informatics system. Its components cover all information handling aspects from compound synthesis via biological testing to preclinical development. design principles are platform and vendor independence, a consistent look feel, complete coverage of the process by custom tailored applications. These include electronic laboratory notebook applications for biology chemistry, tools high-throughput secondary screening evaluation,...

The Raman spectrum of crystalline $\mathrm{Cu}{}_{2}\mathrm{O}$ taken off resonance is reproducible and independent the growth method conditions employed. But, in contrast to most other materials, dominated by infrared active silent lattice modes rather than only allowed phonon mode. We show that this unusual behavior likely caused presence copper vacancies so-called split configuration, a point defect particular $\mathrm{Cu}{}_{2}\mathrm{O}$. reduction symmetry due defects may lift...

Several in-house developed descriptors and our docking tool ActDock were compared with virtual screening on the data set of useful decoys (DUD). The results chemical fingerprint descriptor from ChemAxon original DUD publication. is first published providing active molecules, decoys, references for crystal structures ligand-target complexes. was designed purpose evaluating programs. It contains 2950 compounds against a total 40 target proteins. Furthermore, every ligand 36 structurally...

The Platinum dataset of protein-bound ligand conformations was used to benchmark the ability MMFF94s force field generate bioactive by minimization randomly generated conformers. Torsion angle parameters that generally caused wrong geometries were reparameterized conducting dihedral scans using ab initio calculations at MP2 level. This reparameterization resulted in a systematic improvement conformations.

Molecular complexity is an important characteristic of organic molecules for drug discovery. How to calculate molecular has been discussed in the scientific literature decades. It was known from early on that numbers substructures can be cut out a graph are importance this task. However, it never realized cut-out show self-similarity parent structures. A successive removal one bond and atom returns series fragments with decreasing size. Such shows similar fractal objects. Here we used number...

There has been decades of research on determining and predicting acid dissociation constants (pKa) the tautomer ratios both experimentally theoretically. However, lack an extensive publicly available database measured tautomeric in water nonaqueous solvents poses a challenge for researchers interested theoretical studies related to tautomers. Hereby, we present Tautobase, date best our knowledge, first open-source estimated mainly water, containing 1680 unique pairs.

We describe a toxicity alerting system for uncharacterized compounds, which is based upon comprehensive tables of substructure fragments that are indicative risk. These were derived computationally by analyzing the RTECS database and World Drug Index. provide, free charge, Java applet structure drawing risk assessment. In an independent investigation, we compared classification performance naive Bayesian clustering, k next neighbor classification, support vector machines. To visualize...

Highly homogeneous surface-enhanced Raman scattering substrates were produced on the centimeter scale by annealing solution-processed gold nanoparticles into plasmonic nanoislands.

Wikipedia, the world's largest and most popular encyclopedia is an indispensable source of chemistry information. It contains among others also entries for over 15,000 chemicals including metabolites, drugs, agrochemicals industrial chemicals. To provide easy access to this wealth information we decided develop a substructure similarity search tool chemical structures referenced in Wikipedia.We extracted from Wikipedia implemented web system allowing structure searching on these data. The...

A novel pharmacophore descriptor Flexophore is presented, which considers molecular flexibility when comparing similarities. The a complete reduced graph of the underlying molecule. Its nodes are represented by enhanced MM2 atom types, while edge descriptions encode means histogram node distances in diverse conformer distribution. For two nodes, statistical function derived from Cambridge Crystallographic Database implemented. To assess capability to describe bioactivity space, 350 test data...

A large data set of kinetically plausible proton transfer steps was created. over 48 million steps, between heteroatoms, generated combinatorially from a about 8,000 acids and conjugate bases for which experimental aqueous pKas around room temperature were available. The augmented with 100 estimated highly reactive species important reaction mechanisms. resulting span range -15 to +37. Rate constants at 25 °C using the utilizing simplified Eigen equation without statistical factors. Steps...

The isomerically pure Z ‐ and E ‐pentenylboronates 2 3 were added to ketones under 4 8 kbar pressure resulting in the homoallyl alcohols 10‐13 with different diastereoselectivities. These reactions considered as models for addition of other Z‐ ‐pentenylmetal compounds ketones. diastereoselectivities obtained configurationally undefined pentenyl Grignard ( ) titanium reagents 5,6 is discussed against this background.

We present an efficient algorithm for substructure search in combinatorial libraries defined by synthons, i.e., substructures with connection points. Our method improves on existing approaches introducing powerful heuristics and fast fingerprint screening to quickly eliminate branches of nonmatching combinations synthons. With this, we achieve typical response times a few seconds standard desktop computer searches large like the Enamine REAL Space. published Java source as part OpenChemLib...

In this case study on an essential instrument of modern drug discovery, we summarize our successful efforts in the last four years toward enhancing Actelion screening compound collection. A key organizational step was establishment Compound Library Committee (CLC) September 2013. This cross-functional team consisting computational scientists, medicinal chemists and a biologist endowed with significant annual budget for regular new purchases. Based initial library analysis performed 2013, CLC...

Synthetically accessible chemical spaces provide a valuable source to search for small-molecule analogues or new starting points in drug discovery projects. Having toolbox at hand that can automatically create searchable representations of such using reaction definitions and building blocks as inputs is prerequisite put this approach into practice. Herein, we present tool kit virtual spaces. It part the OpenChemLib, an open-source Cheminformatics kit. Furthermore, demonstrate creation...

In drug discovery, molecules are optimized towards desired properties. this context, machine learning is used for extrapolation in discovery projects. The limits of regression models known. However, a systematic analysis the effectiveness has not yet been performed. response, study examined capabilities six algorithms to extrapolate from 243 datasets. response values calculated datasets were molecular weight, cLogP, and number sp3-atoms. Three experimental set ups chosen values. Shuffled...

Abstract Intramolecular allylboration reactions of (8‐oxo‐2‐octenyl)boronates proceed with excellent diastereoselectivity: the E ‐isomer 1d leads to trans ‐2‐vinylcyclohexanol ( 2 ) 99.5% d.s., corresponding Z‐isomer 3d cyclizes give cis a diastereoselectivity exceeding 99.8%.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCOGNOS: A Beilstein-Type System for Organizing Organic ReactionsJames B. Hendrickson and Thomas SanderCite this: J. Chem. Inf. Comput. Sci. 1995, 35, 2, 251–260Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/ci00024a015https://doi.org/10.1021/ci00024a015research-articleACS PublicationsRequest reuse permissionsArticle Views68Altmetric-Citations15LEARN...