Molecular structure input on the web

A molecule editor, that is program for input and editing of molecules, is an indispensable part of every cheminformatics or molecular processing system. This review focuses on a special type of molecule editors, namely those that are used for molecule structure input on the web. Scientific computing is now moving more and more in the direction of web services and cloud computing, with servers scattered all around the Internet. Thus a web browser has become the universal scientific user interface, and a tool to edit molecules directly within the web browser is essential

Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions

<p>Abstract</p> <p>Background</p> <p>A method to estimate ease of synthesis (synthetic accessibility) of drug-like molecules is needed in many areas of the drug discovery process. The development and validation of such a method that is able to characterize molecule synthetic accessibility as a score between 1 (easy to make) and 10 (very difficult to make) is described in this article.</p> <p>Results</p> <p>The method for estimation of the synthetic accessibility score (SAscore) described here is based on a combination of fragment contributions and a complexity penalty. Fragment contributions have been calculated based on the analysis of one million representative molecules from PubChem and therefore one can say that they capture historical synthetic knowledge stored in this database. The molecular complexity score takes into account the presence of non-standard structural features, such as large rings, non-standard ring fusions, stereocomplexity and molecule size. The method has been validated by comparing calculated SAscores with ease of synthesis as estimated by experienced medicinal chemists for a set of 40 molecules. The agreement between calculated and manually estimated synthetic accessibility is very good with <it>r</it>²= 0.89.</p> <p>Conclusion</p> <p>A novel method to estimate synthetic accessibility of molecules has been developed. This method uses historical synthetic knowledge obtained by analyzing information from millions of already synthesized chemicals and considers also molecule complexity. The method is sufficiently fast and provides results consistent with estimation of ease of synthesis by experienced medicinal chemists. The calculated SAscore may be used to support various drug discovery processes where a large number of molecules needs to be ranked based on their synthetic accessibility, for example when purchasing samples for screening, selecting hits from high-throughput screening for follow-up, or ranking molecules generated by various <it>de novo </it>design approaches.</p

The Adsorption of Atomic Nitrogen on Ru(0001): Geometry and Energetics

The local adsorption geometries of the (2x2)-N and the (sqrt(3)x sqrt(3))R30^o -N phases on the Ru(0001) surface are determined by analyzing low-energy electron diffraction (LEED) intensity data. For both phases, nitrogen occupies the threefold hcp site. The nitrogen sinks deeply into the top Ru layer resulting in a N-Ru interlayer distance of 1.05 AA and 1.10 AA in the (2x2) and the (sqrt(3)x sqrt(3))R30^o unit cell, respectively. This result is attributed to a strong N binding to the Ru surface (Ru--N bond length = 1.93 AA) in both phases as also evidenced by ab-initio calculations which revealed binding energies of 5.82 eV and 5.59 eV, respectively.Comment: 17 pages, 5 figures. Submitted to Chem. Phys. Lett. (October 10, 1996

Oscillatory instabilities during formic acid oxidation on Pt(100), Pt(110) and Pt(111) under potentiostatic control. II. Model calculations

A kinetic model is developed for the electrocatalytic oxidation of formic acid on Pt under potentiostatic control. The model development proceeds stepwise via a simple model of the electrocatalytic CO oxidation. The full model consists of four coupled, nonlinear ordinary differential equations. The scanned and stationary current/outer potential (I/U) behavior, stationary current oscillations, two-parameter bifurcation diagrams and stirring effects are simulated using realistic model parameters. The numerical findings are found to be consistent with the experimental results given by Strasser et al. The model reproduces period-1 as well as mixed-mode oscillations. Furthermore, a mechanistic analysis of the model was performed: two suboscillators are identified whose characteristics allow a plausible interpretation of the observed dynamics. After a classification of the suboscillators into previously described categories, an attempt is made to identify the minimal mechanistic requirements for electrochemical current oscillations

MRI evidence for altered venous drainage and intracranial compliance in mild traumatic brain injury.

To compare venous drainage patterns and associated intracranial hydrodynamics between subjects who experienced mild traumatic brain injury (mTBI) and age- and gender-matched controls. Thirty adult subjects (15 with mTBI and 15 age- and gender-matched controls) were investigated using a 3T MR scanner. Time since trauma was 0.5 to 29 years (mean 11.4 years). A 2D-time-of-flight MR-venography of the upper neck was performed to visualize the cervical venous vasculature. Cerebral venous drainage through primary and secondary channels, and intracranial compliance index and pressure were derived using cine-phase contrast imaging of the cerebral arterial inflow, venous outflow, and the craniospinal CSF flow. The intracranial compliance index is the defined as the ratio of maximal intracranial volume and pressure changes during the cardiac cycle. MR estimated ICP was then obtained through the inverse relationship between compliance and ICP. Compared to the controls, subjects with mTBI demonstrated a significantly smaller percentage of venous outflow through internal jugular veins (60.9±21% vs. controls: 76.8±10%; p = 0.01) compensated by an increased drainage through secondary veins (12.3±10.9% vs. 5.5±3.3%; p<0.03). Mean intracranial compliance index was significantly lower in the mTBI cohort (5.8±1.4 vs. controls 8.4±1.9; p<0.0007). Consequently, MR estimate of intracranial pressure was significantly higher in the mTBI cohort (12.5±2.9 mmHg vs. 8.8±2.0 mmHg; p<0.0007). mTBI is associated with increased venous drainage through secondary pathways. This reflects higher outflow impedance, which may explain the finding of reduced intracranial compliance. These results suggest that hemodynamic and hydrodynamic changes following mTBI persist even in the absence of clinical symptoms and abnormal findings in conventional MR imaging

IN SILICO IDENTIFICATION OF BIOISOSTERIC ANALOGS

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Sticking coefficient for dissociative adsorption of N₂ on Ru single‐crystal surfaces

The dissociative chemisorption of N2 on Ru(0001), Ru(101̄0), and Ru(112̄1) surfaces at 300 K was studied by means of high‐resolution electron energy loss spectroscopy and thermal desorption spectroscopy. The initial sticking coefficient was determined to s0=(1±0.8)×10−12, within the limits of error independent of surface orientation. On Ru(101̄0) and Ru(112̄1) small amounts of N can be dissolved into the subsurface region

Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates

Computational drug design based on artificial intelligence is an emerging research area. At the time of writing this paper, the world suffers from an outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus replication is via protease inhibition. We propose an evolutionary multi-objective algorithm (EMOA) to design potential protease inhibitors for SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA maximizes the binding of candidate ligands to the protein using the docking tool QuickVina 2, while at the same time taking into account further objectives like drug-likeliness or the fulfillment of filter constraints. The experimental part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202

Small Force, Big Impact: Next Generation Organ-on-a-Chip Systems Incorporating Biomechanical Cues

Mechanobiology-on-a-chip is a growing field focusing on how mechanical inputs modulate physico-chemical output in microphysiological systems. It is well known that biomechanical cues trigger a variety of molecular events and adjustment of mechanical forces is therefore essential for mimicking in vivo physiologies in organon-a-chip technology. Biomechanical inputs in organ-on-a-chip systems can range from variations in extracellular matrix type and stiffness and applied shear stresses to active stretch/strain or compression forces using integrated flexible membranes. The main advantages of these organ-on-a-chip systems are therefore (a) the control over spatiotemporal organization of in vivo-like tissue architectures, (b) the ability to precisely control the amount, duration and intensity of the biomechanical stimuli, and (c) the capability of monitoring in real time the effects of applied mechanical forces on cell, tissue and organ functions. Consequently, over the last decade a variety of microfluidic devices have been introduced to recreate physiological microenvironments that also account for the influence of physical forces on biological functions. In this review we present recent advances in mechanobiological lab-on-a-chip systems and report on lessons learned from these current mechanobiological models. Additionally, future developments needed to engineer next-generation physiological and pathological organ-on-a-chip models are discussed

Supersymmetric black holes in 2D dilaton supergravity: baldness and extremality

We present a systematic discussion of supersymmetric solutions of 2D dilaton supergravity. In particular those solutions which retain at least half of the supersymmetries are ground states with respect to the bosonic Casimir function (essentially the ADM mass). Nevertheless, by tuning the prepotential appropriately, black hole solutions may emerge with an arbitrary number of Killing horizons. The absence of dilatino and gravitino hair is proven. Moreover, the impossibility of supersymmetric dS ground states and of nonextremal black holes is confirmed, even in the presence of a dilaton. In these derivations the knowledge of the general analytic solution of 2D dilaton supergravity plays an important role. The latter result is addressed in the more general context of gPSMs which have no supergravity interpretation. Finally it is demonstrated that the inclusion of non-minimally coupled matter, a step which is already nontrivial by itself, does not change these features in an essential way.Comment: 30 pages, LaTeX, v2: mayor revision (rearranged title, shortened abstract, revised introduction, inserted section from appendix to main text, added subsection with new material on non-SUGRA gPSMs, added clarifying remarks at some places, updated references); v3: corrected minor misprints, added note with a new referenc