The octet rule in chemical space: Generating virtual molecules

We present a generator of virtual molecules that selects valid chemistry on the basis of the octet rule. Also, we introduce a mesomer group key that allows a fast detection of duplicates in the generated structures. Compared to existing approaches, our model is simpler and faster, generates new chemistry and avoids invalid chemistry. Its versatility is illustrated by the correct generation of molecules containing third-row elements and a surprisingly adept handling of complex boron chemistry. Without any empirical parameters, our model is designed to be valid also in unexplored regions of chemical space. One first unexpected finding is the high prevalence of dipolar structures among generated molecules.Comment: 24 pages, 10 figure

Metadaten: Schlüssel zur Nutzung von Informationssystemen

Zunehmend werden Informationssysteme aufgebaut zur Gewinnung von Informationen, die der Entscheidungsfindung dienen. Damit stellt sich jedoch die Frage, wie bei ständig zunehmendem Informationsangebot die entscheidungsrelevanten Datenbestände ausgewählt werden können. Wenn man Informationssysteme als Gesamtheit von Daten und Methoden definiert, so sind Metadaten der Bestandteil des Systems, der die dort vorgehaltenen Daten beschreibt. Sie sollen als Leitinstrument bei der Nutzung des Informationssystems fungieren. Informationssysteme dienen der Durchführung von Untersuchungen. Die Arbeitsschritte bei dieser Aufgabe werden durch das Adäquations- und Interpretationsproblem beschrieben. Metadaten sollen den Nutzer von Informationssystemen bei der Durchführung dieser Arbeitsschritte möglichst weitgehend unterstützen. Inwieweit sie bei den einzelnen Arbeitsschritten Hilfestellung geben können und wie sie für diesen Zweck aufgebaut sein sollten, wird in diesem Beitrag allgemein und am Beispiel der Sozialhilfestatistik sowie der Umweltstatistik gezeigt --

Assessment of numerical optimization algorithms for the development of molecular models

In the pursuit to study the parameterization problem of molecular models with a broad perspective, this paper is focused on an isolated aspect: It is investigated, by which algorithms parameters can be best optimized simultaneously to different types of target data (experimental or theoretical) over a range of temperatures with the lowest number of iteration steps. As an example, nitrogen is regarded, where the intermolecular interactions are well described by the quadrupolar two-center Lennard-Jones model that has four state-independent parameters. The target data comprise experimental values for saturated liquid density, enthalpy of vaporization, and vapor pressure. For the purpose of testing algorithms, molecular simulations are entirely replaced by fit functions of vapor-liquid equilibrium (VLE) properties from the literature to assess efficiently the diverse numerical optimization algorithms investigated, being state-of-the-art gradient-based methods with very good convergency qualities. Additionally, artificial noise was superimposed onto the VLE fit results to evaluate the numerical optimization algorithms so that the calculation of molecular simulation data was mimicked. Large differences in the behavior of the individual optimization algorithms are found and some are identified to be capable to handle noisy function values

Economic simplex optimization for broad range property prediction: Strengths and weaknesses of an automated approach for tailoring of parameters

The need for predicting physical compound properties supplementing experimental data is considerable. Nowadays a wide range of classical simulation techniques is available for computing a multitude of such properties with acceptable effort. We here give a field report about our approach, which was to fit an initial model to a single point in the phase diagram. Byway of accessing commonly available experimental valueswe developed a compound-specific force field via simplex optimization. For predicting the desired properties of the novel model we did engage classical equilibrium as well as reverse non-equilibrium molecular dynamics in combination with Monte Carlo methods and report here the performance of these methods in detail for the example compound ethylene oxide. We find that the new model describes the experimentally observed behavior of the test compound ethylene oxide (EO) very well in the molecular dynamics section. However, when applying the simplex optimized model to the Monte Carlo section, the limits of transferability become apparent

Folding and unfolding characteristics of short beta strand peptides under different environmental conditions and starting configurations

We analyze the effect of different environmental conditions, sequence lengths and starting configurations on the folding and unfolding pathways of small peptides exhibiting beta turns. We use chignolin and a sequence of peptide G as examples. A variety of different analysis tools allows us to characterize the changes in the folding pathways. It is observed that different harmonic modes dominate not only for different conditions but also for different starting points. The modes remain essentially very similar but their relative importance varies. A detailed analysis from diverse viewpoints including the influence of the particular amino acid sequence, conformational aspects as well as the associated motions yields a global picture that is consistent with experimental evidence and theoretical studies published elsewhere. Patterns of modes that remain stable over a range of temperatures might serve as an additional diagnostic to identify conformations that have reliably adopted a native fold. This could aid in reconstructing the folding process of a complete protein by identifying conformationally determined regions

Insights into the Folding of Disulfide-Rich μ‑Conotoxins

The study of protein conformations using molecular dynamics (MD) simulations has been in place for decades. A major contribution to the structural stability and native conformation of a protein is made by the primary sequence and disulfide bonds formed during the folding process. Here, we investigated μ-conotoxins GIIIA, KIIIA, PIIIA, SIIIA, and SmIIIA as model peptides possessing three disulfide bonds. Their NMR structures were used for MD simulations in a novel approach studying the conformations between the folded and the unfolded states by systematically breaking the distinct disulfide bonds and monitoring the conformational stability of the peptides. As an outcome, the use of a combination of the existing knowledge and results from the simulations to classify the studied peptides within the extreme models of disulfide folding pathways, namely the bovine pancreatic trypsin inhibitor pathway and the hirudin pathway, is demonstrated. Recommendations for the design and synthesis of cysteine-rich peptides with a reduced number of disulfide bonds conclude the study

On the Nature of Interactions between Ionic Liquids and Small Amino-Acid-Based Biomolecules

During the last decade, ionic liquids (ILs) have revealed promising properties and applications in many research fields, including biotechnology and biological sciences. The focus of this contribution is to give a critical review of the phenomena observed and current knowledge of the interactions occurring on a molecular basis. As opposed to the huge advances made in understanding the properties of proteins in ILs, complementary investigations dealing with interactions between ILs and peptides or oligopeptides are underrepresented and are mostly only of phenomenological nature. However, the field has received more attention in the last few years. This Review features a meta-analysis of the available data and findings and should, therefore, provide a basis for a scientifically profound understanding of the nature and mechanisms of interactions between ILs and structured or nonstructured peptides. Fundamental aspects of the interactions between different peptides/oligopep tides and ILs are complemented by sections on the experimental (spectroscopy, structural biology) and theoretical (computational chemistry) possibilities to explain the phenomena reported so far in the literature. In effect, this should lead to the development of novel applications and support the understanding of IL-solute interactions in general. Ionic liquid interactions: This Review gives a comprehensive overview of the current knowledge on the molecular basis and fundamental aspects of the interactions between amino acid-based molecules and ionic liquids, with focus on peptides and miniproteins. Technical (spectroscopy, structural biology) and theoretical (computational chemistry) prerequisites to explain the phenomena reported so far are critically assessed