Search results for "Computer-aided"
showing 10 items of 416 documents
Advances on mechanics, design engineering and manufacturing
2018
The theme of the present editorial is dedicated to the“Advances on Mechanics, Design Engineering and Manufac-turing” that emerge in different engineering and architecturalfields.The theme has been chosen as leitmotiv of a series ofevents that have been organized by three societies operatingin Italy, Spain and France, respectively: ADM (Associ-azione nazionale Disegno e Metodi dell’ingegneria indus-triale), INGEGRAF (Asociación Española de IngenieríaGráfica and AIP-PRIMECA (Ateliers Inter-établissementsde Productique—Pôles de Resources Informatiques pour laMECAnique). Since 2014, a series of JCM conferences havebeen organized. JCM is the acronym of “Joint Conference onMechanics, Design Engin…
Intelligent agents for feature modelling in computer aided design
2017
Abstract CAD modelling can be referred to as the process of generating an integrated multiple view model as a representation of multiple views of engineering design. In many situations, a change in the model of one view may conflict with the models of other views. In such situations, the model of some views needs to be adapted in order to make all models consistent. Thus, CAD models should be capable of adapting themselves to new situations. Recently, agent based technologies have been considered in order to increase both knowledge level and intelligence of real and virtual objects. The contribution of this paper consists in introducing the intelligent agents in intelligent CAD modelling. T…
Global sensitivity analysis in welding simulations -- what are the material data you really need ?
2011
In this paper, the sensitivity analysis methodology is applied to numerical welding simulation in order to rank the importance of input variables on the outputs of the code like distorsions or residual stresses. The numerical welding simulation uses the finite element method, with a thermal computation followed by a mechanical one. Classically, a local sensitivity analysis is performed, hence the validity of the results is limited to the neighbourhood of a nominal point, and cross effects cannot be detected. This study implements a global sensitivity analysis which allows to screen the whole material space of the steel family mechanical properties. A set of inputs of the mechanical model-ma…
Rocker: Open source, easy-to-use tool for AUC and enrichment calculations and ROC visualization
2016
Receiver operating characteristics (ROC) curve with the calculation of area under curve (AUC) is a useful tool to evaluate the performance of biomedical and chemoinformatics data. For example, in virtual drug screening ROC curves are very often used to visualize the efficiency of the used application to separate active ligands from inactive molecules. Unfortunately, most of the available tools for ROC analysis are implemented into commercially available software packages, or are plugins in statistical software, which are not always the easiest to use. Here, we present Rocker, a simple ROC curve visualization tool that can be used for the generation of publication quality images. Rocker also…
Conf-VLKA: A structure-based revisitation of the Virtual Lock-and-key Approach
2016
In a previous work, we developed the in house Virtual Lock-and-Key Approach (VLKA) in order to evaluate target assignment starting from molecular descriptors calculated on known inhibitors used as an information source. This protocol was able to predict the correct biological target for the whole dataset with a good degree of reliability (80%), and proved experimentally, which was useful for the target fishing of unknown compounds. In this paper, we tried to remodel the previous in house developed VLKA in a more sophisticated one in order to evaluate the influence of 3D conformation of ligands on the accuracy of the prediction. We applied the same previous algorithm of scoring and ranking b…
Identification of estrogen receptor α ligands with virtual screening techniques.
2016
Utilization of computer-aided molecular discovery methods in virtual screening (VS) is a cost-effective approach to identify novel bioactive small molecules. Unfortunately, no universal VS strategy can guarantee high hit rates for all biological targets, but each target requires distinct, fine-tuned solutions. Here, we have studied in retrospective manner the effectiveness and usefulness of common pharmacophore hypothesis, molecular docking and negative image-based screening as potential VS tools for a widely applied drug discovery target, estrogen receptor α (ERα). The comparison of the methods helps to demonstrate the differences in their ability to identify active molecules. For example,…
Discovery and Biological Evaluation of Potent and Selective N-Methylene Saccharin-Derived Inhibitors for Rhomboid Intramembrane Proteases
2017
Rhomboids are intramembrane serine proteases and belong to the group of structurally and biochemically most comprehensively characterized membrane proteins. They are highly conserved and ubiquitously distributed in all kingdoms of life and function in a wide range of biological processes, including epidermal growth factor signaling, mitochondrial dynamics, and apoptosis. Importantly, rhomboids have been associated with multiple diseases, including Parkinson's disease, type 2 diabetes, and malaria. However, despite a thorough understanding of many structural and functional aspects of rhomboids, potent and selective inhibitors of these intramembrane proteases are still not available. In this …
Recent advances on CDK inhibitors: An insight by means of in silico methods
2017
The cyclin dependent kinases (CDKs) are a small family of serine/threonine protein kinases that can act as a potential therapeutic target in several proliferative diseases, including cancer. This short review is a survey on the more recent research progresses in the field achieved by using in silico methods. All the "armamentarium" available to the medicinal chemists (docking protocols and molecular dynamics, fragment-based, de novo design, virtual screening, and QSAR) has been employed to the discovery of new, potent, and selective inhibitors of cyclin dependent kinases. The results cited herein can be useful to understand the nature of the inhibitor-target interactions, and furnish an ins…
QuBiLS-MAS, open source multi-platform software for atom- and bond-based topological (2D) and chiral (2.5D) algebraic molecular descriptors computati…
2017
Background In previous reports, Marrero-Ponce et al. proposed algebraic formalisms for characterizing topological (2D) and chiral (2.5D) molecular features through atom- and bond-based ToMoCoMD-CARDD (acronym for Topological Molecular Computational Design-Computer Aided Rational Drug Design) molecular descriptors. These MDs codify molecular information based on the bilinear, quadratic and linear algebraic forms and the graph-theoretical electronic-density and edge-adjacency matrices in order to consider atom- and bond-based relations, respectively. These MDs have been successfully applied in the screening of chemical compounds of different therapeutic applications ranging from antimalarials…
Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives
2018
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-b-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced 62% HSD1 inhibition at 5 mM and, furthermore, three of them produced 68% inhibition at 1 mM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases. Most of the analogues are only modestly active with 17-b-hydroxysteroid dehydrogenase 2 – a requirement for lowe…