The benefits of in silico modeling to identify possible small-molecule drugs and their off-target interactions

Accepted for publication in a future issue of Future Medicinal Chemistry.The research into the use of small molecules as drugs continues to be a key driver in the development of molecular databases, computer-aided drug design software and collaborative platforms. The evolution of computational approaches is driven by the essential criteria that a drug molecule has to fulfill, from the affinity to targets to minimal side effects while having adequate absorption, distribution, metabolism, and excretion (ADME) properties. A combination of ligand- and structure-based drug development approaches is already used to obtain consensus predictions of small molecule activities and their off-target interactions. Further integration of these methods into easy-to-use workflows informed by systems biology could realize the full potential of available data in the drug discovery and reduce the attrition of drug candidates.Peer reviewe

Updates in metabolomics tools and resources: 2014-2015

Data processing and interpretation represent the most challenging and time-consuming steps in high-throughput metabolomic experiments, regardless of the analytical platforms (MS or NMR spectroscopy based) used for data acquisition. Improved machinery in metabolomics generates increasingly complex datasets that create the need for more and better processing and analysis software and in silico approaches to understand the resulting data. However, a comprehensive source of information describing the utility of the most recently developed and released metabolomics resources—in the form of tools, software, and databases—is currently lacking. Thus, here we provide an overview of freely-available, and open-source, tools, algorithms, and frameworks to make both upcoming and established metabolomics researchers aware of the recent developments in an attempt to advance and facilitate data processing workflows in their metabolomics research. The major topics include tools and researches for data processing, data annotation, and data visualization in MS and NMR-based metabolomics. Most in this review described tools are dedicated to untargeted metabolomics workflows; however, some more specialist tools are described as well. All tools and resources described including their analytical and computational platform dependencies are summarized in an overview Table

The Origins of Computational Mechanics: A Brief Intellectual History and Several Clarifications

The principle goal of computational mechanics is to define pattern and structure so that the organization of complex systems can be detected and quantified. Computational mechanics developed from efforts in the 1970s and early 1980s to identify strange attractors as the mechanism driving weak fluid turbulence via the method of reconstructing attractor geometry from measurement time series and in the mid-1980s to estimate equations of motion directly from complex time series. In providing a mathematical and operational definition of structure it addressed weaknesses of these early approaches to discovering patterns in natural systems. Since then, computational mechanics has led to a range of results from theoretical physics and nonlinear mathematics to diverse applications---from closed-form analysis of Markov and non-Markov stochastic processes that are ergodic or nonergodic and their measures of information and intrinsic computation to complex materials and deterministic chaos and intelligence in Maxwellian demons to quantum compression of classical processes and the evolution of computation and language. This brief review clarifies several misunderstandings and addresses concerns recently raised regarding early works in the field (1980s). We show that misguided evaluations of the contributions of computational mechanics are groundless and stem from a lack of familiarity with its basic goals and from a failure to consider its historical context. For all practical purposes, its modern methods and results largely supersede the early works. This not only renders recent criticism moot and shows the solid ground on which computational mechanics stands but, most importantly, shows the significant progress achieved over three decades and points to the many intriguing and outstanding challenges in understanding the computational nature of complex dynamic systems.Comment: 11 pages, 123 citations; http://csc.ucdavis.edu/~cmg/compmech/pubs/cmr.ht