Notes on the Treatment of Charged Particles for Studying Cyclotide/Membrane Interactions with Dissipative Particle Dynamics

Different charge treatment approaches are examined for cyclotide-induced plasma membrane disruption by lipid extraction studied with dissipative particle dynamics. A pure Coulomb approach with truncated forces tuned to avoid individual strong ion pairing still reveals hidden statistical pairing effects that may lead to artificial membrane stabilization or distortion of cyclotide activity depending on the cyclotide’s charge state. While qualitative behavior is not affected in an apparent manner, more sensitive quantitative evaluations can be systematically biased. The findings suggest a charge smearing of point charges by an adequate charge distribution. For large mesoscopic simulation boxes, approximations for the Ewald sum to account for mirror charges due to periodic boundary conditions are of negligible influence

CDK-Taverna: an open workflow environment for cheminformatics

<p>Abstract</p> <p>Background</p> <p>Small molecules are of increasing interest for bioinformatics in areas such as metabolomics and drug discovery. The recent release of large open access chemistry databases generates a demand for flexible tools to process them and discover new knowledge. To freely support open science based on these data resources, it is desirable for the processing tools to be open source and available for everyone.</p> <p>Results</p> <p>Here we describe a novel combination of the workflow engine Taverna and the cheminformatics library Chemistry Development Kit (CDK) resulting in a open source workflow solution for cheminformatics. We have implemented more than 160 different workers to handle specific cheminformatics tasks. We describe the applications of CDK-Taverna in various usage scenarios.</p> <p>Conclusions</p> <p>The combination of the workflow engine Taverna and the Chemistry Development Kit provides the first open source cheminformatics workflow solution for the biosciences. With the Taverna-community working towards a more powerful workflow engine and a more user-friendly user interface, CDK-Taverna has the potential to become a free alternative to existing proprietary workflow tools.</p

New developments on the cheminformatics open workflow environment CDK-Taverna

<p>Abstract</p> <p>Background</p> <p>The computational processing and analysis of small molecules is at heart of cheminformatics and structural bioinformatics and their application in e.g. metabolomics or drug discovery. Pipelining or workflow tools allow for the Lego™-like, graphical assembly of I/O modules and algorithms into a complex workflow which can be easily deployed, modified and tested without the hassle of implementing it into a monolithic application. The CDK-Taverna project aims at building a free open-source cheminformatics pipelining solution through combination of different open-source projects such as Taverna, the Chemistry Development Kit (CDK) or the Waikato Environment for Knowledge Analysis (WEKA). A first integrated version 1.0 of CDK-Taverna was recently released to the public.</p> <p>Results</p> <p>The CDK-Taverna project was migrated to the most up-to-date versions of its foundational software libraries with a complete re-engineering of its worker's architecture (version 2.0). 64-bit computing and multi-core usage by paralleled threads are now supported to allow for fast in-memory processing and analysis of large sets of molecules. Earlier deficiencies like workarounds for iterative data reading are removed. The combinatorial chemistry related reaction enumeration features are considerably enhanced. Additional functionality for calculating a natural product likeness score for small molecules is implemented to identify possible drug candidates. Finally the data analysis capabilities are extended with new workers that provide access to the open-source WEKA library for clustering and machine learning as well as training and test set partitioning. The new features are outlined with usage scenarios.</p> <p>Conclusions</p> <p>CDK-Taverna 2.0 as an open-source cheminformatics workflow solution matured to become a freely available and increasingly powerful tool for the biosciences. The combination of the new CDK-Taverna worker family with the already available workflows developed by a lively Taverna community and published on myexperiment.org enables molecular scientists to quickly calculate, process and analyse molecular data as typically found in e.g. today's systems biology scenarios.</p

From curve fitting to machine learning: an illustrative guide to scientific data analysis and computational intelligence

This successful book provides in its second edition an interactive and illustrative guide from two-dimensional curve fitting to multidimensional clustering and machine learning with neural networks or support vector machines. Along the way topics like mathematical optimization or evolutionary algorithms are touched. All concepts and ideas are outlined in a clear cut manner with graphically depicted plausibility arguments and a little elementary mathematics. The major topics are extensively outlined with exploratory examples and applications. The primary goal is to be as illustrative as possible without hiding problems and pitfalls but to address them. The character of an illustrative cookbook is complemented with specific sections that address more fundamental questions like the relation between machine learning and human intelligence. All topics are completely demonstrated with the computing platform Mathematica and the Computational Intelligence Packages (CIP), a high-level function library developed with Mathematica's programming language on top of Mathematica's algorithms. CIP is open-source and the detailed code used throughout the book is freely accessible. The target readerships are students of (computer) science and engineering as well as scientific practitioners in industry and academia who deserve an illustrative introduction. Readers with programming skills may easily port or customize the provided code. "'From curve fitting to machine learning' is ... a useful book. ... It contains the basic formulas of curve fitting and related subjects and throws in, what is missing in so many books, the code to reproduce the results. All in all this is an interesting and useful book both for novice as well as expert readers. For the novice it is a good introductory book and the expert will appreciate the many examples and working code." Leslie A. Piegl (Review of the first edition, 2012)

From Curve Fitting to Machine Learning

The analysis of experimental data is at heart of science from its beginnings. But it was the advent of digital computers that allowed the execution of highly non-linear and increasingly complex data analysis procedures - methods that were completely unfeasible before. Non-linear curve fitting, clustering and machine learning belong to these modern techniques which are a further step towards computational intelligence. The goal of this book is to provide an interactive and illustrative guide to these topics. It concentrates on the road from two dimensional curve fitting to multidimensional clu

Complex formation of Cucurbit[6]uril with DABCO and DABCO derivatives: An experimental and DFT study

The complex formation of Cucurbit[6]uril with DABCO and DABCO derivatives in solution has been studied using calorimetric titrations. For a better understanding of factors influencing the complex formation, several DABCO derivatives have been synthesized. All compounds have been characterized. Inclusion complex formation could not be observed. Even with dumbbell derivatives of DABCO threading through the Cucurbit[6]uril cavity does not occur. As a result, no rotaxanes have been formed in solution. These results are in accordance with DFT calculations

DECIMER - Towards Deep Learning for Chemical Image Recognition

The automatic recognition of chemical structure diagrams from the literature is an indispensable component of workflows to re-discover information about chemicals and to make it available in open-access databases. Here we report preliminary findings in our development of DECIMER (Deep lEarning for Chemical ImagE Recognition), a deep learning method based on existing show-and-tell deep neural networks which makes very few assumptions about the structure of the underlying problem. The training state reported here does not yet rival the performance of existing traditional approaches, but we present evidence that our method will reach a comparable detection power with sufficient training time. Training success of DECIMER depends on the input data representation: DeepSMILES are clearly superior over SMILES and we have preliminary indication that the recently reported SELFIES outperform DeepSMILES. An extrapolation of our results towards larger training data sizes suggest that we might be able to achieve >90% accuracy with about 60 to 100 million training structures, so that training can be completed within several months on a single GPU. This work is completely based on open-source software and open data and is available to the general public for any purpose

STOUT: SMILES to IUPAC Names Using Neural Machine Translation

Chemical compounds can be identified through a graphical depiction, a suitable string representation, or a chemical name. A universally accepted naming scheme for chemistry was established by the International Union of Pure and Applied Chemistry (IUPAC) based on a set of rules. Due to the complexity of this rule set a correct chemical name assignment remains challenging for human beings and there are only a few rule-based cheminformatics toolkits available that support this task in an automated manner. Here we present STOUT (SMILES-TO-IUPAC-name translator), a deep-learning neural machine translation approach to generate the IUPAC name for a given molecule from its SMILES string as well as the reverse translation, i.e., predicting the SMILES string from the IUPAC name. The open system demonstrates a test accuracy of about 90% correct predictions, also incorrect predictions show a remarkable similarity between true and predicted compounds.</p