Application of the SwissDrugDesign Online Resources in Virtual Screening.

SwissDrugDesign is an important initiative led by the Molecular Modeling Group of the SIB Swiss Institute of Bioinformatics. This project provides a collection of freely available online tools for computer-aided drug design. Some of these web-based methods, i.e., SwissSimilarity and SwissTargetPrediction, were especially developed to perform virtual screening, while others such as SwissADME, SwissDock, SwissParam and SwissBioisostere can find applications in related activities. The present review aims at providing a short description of these methods together with examples of their application in virtual screening, where SwissDrugDesign tools successfully supported the discovery of bioactive small molecules

Modelling electric vehicles use: a survey on the methods

In the literature electric vehicle use is modelled using of a variety of approaches in power systems, energy and environmental analyses as well as in travel demand analysis. This paper provides a systematic review of these diverse approaches using a twofold classification of electric vehicle use representation, based on the time scale and on substantive differences in the modelling techniques. For time of day analysis of demand we identify activity-based modelling (ABM) as the most attractive because it provides a framework amenable for integrated cross-sector analyses, required for the emerging integration of the transport and electricity network. However, we find that the current examples of implementation of AMB simulation tools for EV-grid interaction analyses have substantial limitations. Amongst the most critical there is the lack of realism how charging behaviour is represented

SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules.

SwissTargetPrediction is a web tool, on-line since 2014, that aims to predict the most probable protein targets of small molecules. Predictions are based on the similarity principle, through reverse screening. Here, we describe the 2019 version, which represents a major update in terms of underlying data, backend and web interface. The bioactivity data were updated, the model retrained and similarity thresholds redefined. In the new version, the predictions are performed by searching for similar molecules, in 2D and 3D, within a larger collection of 376 342 compounds known to be experimentally active on an extended set of 3068 macromolecular targets. An efficient backend implementation allows to speed up the process that returns results for a druglike molecule on human proteins in 15-20 s. The refreshed web interface enhances user experience with new features for easy input and improved analysis. Interoperability capacity enables straightforward submission of any input or output molecule to other on-line computer-aided drug design tools, developed by the SIB Swiss Institute of Bioinformatics. High levels of predictive performance were maintained despite more extended biological and chemical spaces to be explored, e.g. achieving at least one correct human target in the top 15 predictions for >70% of external compounds. The new SwissTargetPrediction is available free of charge (www.swisstargetprediction.ch)

SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.

To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours

SwissTargetPrediction: a web server for target prediction of bioactive small molecules.

Bioactive small molecules, such as drugs or metabolites, bind to proteins or other macro-molecular targets to modulate their activity, which in turn results in the observed phenotypic effects. For this reason, mapping the targets of bioactive small molecules is a key step toward unraveling the molecular mechanisms underlying their bioactivity and predicting potential side effects or cross-reactivity. Recently, large datasets of protein-small molecule interactions have become available, providing a unique source of information for the development of knowledge-based approaches to computationally identify new targets for uncharacterized molecules or secondary targets for known molecules. Here, we introduce SwissTargetPrediction, a web server to accurately predict the targets of bioactive molecules based on a combination of 2D and 3D similarity measures with known ligands. Predictions can be carried out in five different organisms, and mapping predictions by homology within and between different species is enabled for close paralogs and orthologs. SwissTargetPrediction is accessible free of charge and without login requirement at http://www.swisstargetprediction.ch

Modelling the influence of peers’ attitudes on choice behaviour: theory and empirical application on electric vehicle preferences

While the importance of social influence on transport-related choices is commonly acknowledged within the transport and travel behaviour research community, there remain several challenges in modelling influence in practice. This paper proposes a new analytical approach to measure the effects of attitudes of peers on the decision making process of the individual. Indeed, while most of the previous literature focused its attention on capturing conformity to a certain real or hypothetical choice, we investigate the subtle effect of attitudes that underlies this choice. Specifically, the suggested measure enables us to model the correlated effect that might indirectly affect the individual’s choice within a social group. It combines detailed information on the attitudes in the individual’s social network and the social proximity of the individuals in the social network. To understand its behavioural implications on the individual’s choice, the individual’s peer attitude variable is tested in different components of a hybrid choice model. Our results show that the inclusion of this variable indirectly affects the decision making process of the individual as the peers’ attitudes are significantly related to the latent attitude of the individual. On the other hand, it does not seem to directly affect the utility of an alternative as a source of systematic heterogeneity nor does it work as a manifestation of the latent variable, i.e. as an indicator

Attracting cavities for docking. Replacing the rough energy landscape of the protein by a smooth attracting landscape.

Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure-based computer-aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently replacing the rough potential energy hypersurface of the protein by a smooth attracting potential driving the ligands into protein cavities. The actual protein energy landscape is reintroduced in a second step to refine the ligand position. The scoring function of Attracting Cavities is based on the CHARMM force field and the FACTS solvation model. The approach was tested on the 85 experimental ligand-protein structures included in the Astex diverse set and achieved a success rate of 80% in reproducing the experimental binding mode starting from a completely randomized ligand conformer. The algorithm thus compares favorably with current state-of-the-art docking programs

Using digital social market applications to incentivise active travel: Empirical analysis of a smart city initiative

Information and communication technologies (ICTs), such as mobile communication networks, and behaviour-based approaches for citizen engagement play a key role in making future cities sustainable and tackling persistent problems in high-density urban areas. In the context of Sharing Cities, an EU-funded programme aiming to deliver smart city solutions in areas such as citizen participation and infrastructure improvements of buildings and mobility, a prominent intervention has been the deployment and monitoring of a Digital Social Market (DSM) tool in Milan (Italy). The DSM allows cities to engage with residents and encourage sustainable behaviours by offering non-monetary rewards. This paper aims to evaluate the effectiveness of the DSM approach to promote active travel (cycling and walking) by analysing the data collected through the app as well as through participant surveys. Our model results show that a broader engagement with the DSM app (number of claps to posts, number of posts made, non-monetary rewards earned by participating in non-travel events) is positively correlated with the monitored level of active travel. Lifestyles, attitudes, and social influence also explain the variability in cycling and walking. This highlights the importance of investigating these factors when replicating such initiatives on a large scale

Increasing the proportion of healthier foods available with and without reducing portion sizes and energy purchased in worksite cafeterias:protocol for a stepped-wedge randomised controlled trial

BACKGROUND: Overconsumption of energy from food contributes to high rates of overweight and obesity in many populations. A promising set of interventions tested in pilot studies in worksite cafeterias, suggests energy intake may be reduced by increasing the proportion of healthier - i.e. lower energy - food options available, and decreasing portion sizes. The current study aims to assess the impact on energy purchased of i. increasing the proportion of lower energy options available; ii. combining this with reducing portion sizes, in a full trial. METHODS: A stepped-wedge randomised controlled trial in 19 worksite cafeterias, where the proportion of lower energy options available in targeted food categories (including main meals, snacks, and cold drinks) will be increased; and combined with reduced portion sizes. The primary outcome is total energy (kcal) purchased from targeted food categories using a pooled estimate across all sites. Follow-up analyses will test whether the impact on energy purchased varies according to the extent of intervention implementation. DISCUSSION: This study will provide the most reliable estimate to date of the effect sizes of two promising interventions for reducing energy purchased in worksite cafeterias. TRIAL REGISTRATION: The study was prospectively registered on ISRCTN (date: 24.05.19; TRN: ISRCTN87225572; doi: https://doi.org/10.1186/ISRCTN87225572)