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Sample records for 3d molecular descriptors

  1. Structure/response correlations and similarity/diversity analysis by GETAWAY descriptors. 2. Application of the novel 3D molecular descriptors to QSAR/QSPR studies.

    PubMed

    Consonni, Viviana; Todeschini, Roberto; Pavan, Manuela; Gramatica, Paola

    2002-01-01

    In a previous paper the theory of the new molecular descriptors called GETAWAY (GEometry, Topology, and Atom-Weights AssemblY) was explained. These descriptors have been proposed with the aim of matching 3D-molecular geometry, atom relatedness, and chemical information. In this paper prediction ability in structure-property correlations of GETAWAY descriptors has been tested extensively by analyzing the regressions of these descriptors for selected properties of some reference compound classes. Moreover, the general performance of the new descriptors in QSAR/QSPR has been evaluated with respect to other well-known sets of molecular descriptors.

  2. Molecular Descriptors

    NASA Astrophysics Data System (ADS)

    Consonni, Viviana; Todeschini, Roberto

    In the last decades, several scientific researches have been focused on studying how to encompass and convert - by a theoretical pathway - the information encoded in the molecular structure into one or more numbers used to establish quantitative relationships between structures and properties, biological activities, or other experimental properties. Molecular descriptors are formally mathematical representations of a molecule obtained by a well-specified algorithm applied to a defined molecular representation or a well-specified experimental procedure. They play a fundamental role in chemistry, pharmaceutical sciences, environmental protection policy, toxicology, ecotoxicology, health research, and quality control. Evidence of the interest of the scientific community in the molecular descriptors is provided by the huge number of descriptors proposed up today: more than 5000 descriptors derived from different theories and approaches are defined in the literature and most of them can be calculated by means of dedicated software applications. Molecular descriptors are of outstanding importance in the research fields of quantitative structure-activity relationships (QSARs) and quantitative structure-property relationships (QSPRs), where they are the independent chemical information used to predict the properties of interest. Along with the definition of appropriate molecular descriptors, the molecular structure representation and the mathematical tools for deriving and assessing models are other fundamental components of the QSAR/QSPR approach. The remarkable progress during the last few years in chemometrics and chemoinformatics has led to new strategies for finding mathematical meaningful relationships between the molecular structure and biological activities, physico-chemical, toxicological, and environmental properties of chemicals. Different approaches for deriving molecular descriptors here reviewed and some of the most relevant descriptors are presented in

  3. 3D object recognition based on local descriptors

    NASA Astrophysics Data System (ADS)

    Jakab, Marek; Benesova, Wanda; Racev, Marek

    2015-01-01

    In this paper, we propose an enhanced method of 3D object description and recognition based on local descriptors using RGB image and depth information (D) acquired by Kinect sensor. Our main contribution is focused on an extension of the SIFT feature vector by the 3D information derived from the depth map (SIFT-D). We also propose a novel local depth descriptor (DD) that includes a 3D description of the key point neighborhood. Thus defined the 3D descriptor can then enter the decision-making process. Two different approaches have been proposed, tested and evaluated in this paper. First approach deals with the object recognition system using the original SIFT descriptor in combination with our novel proposed 3D descriptor, where the proposed 3D descriptor is responsible for the pre-selection of the objects. Second approach demonstrates the object recognition using an extension of the SIFT feature vector by the local depth description. In this paper, we present the results of two experiments for the evaluation of the proposed depth descriptors. The results show an improvement in accuracy of the recognition system that includes the 3D local description compared with the same system without the 3D local description. Our experimental system of object recognition is working near real-time.

  4. Flexible 3D pharmacophores as descriptors of dynamic biological space.

    PubMed

    Nettles, James H; Jenkins, Jeremy L; Williams, Chris; Clark, Alex M; Bender, Andreas; Deng, Zhan; Davies, John W; Glick, Meir

    2007-10-01

    Development of a pharmacophore hypothesis related to small-molecule activity is pivotal to chemical optimization of a series, since it defines features beneficial or detrimental to activity. Although crystal structures may provide detailed 3D interaction information for one molecule with its receptor, docking a different ligand to that model often leads to unreliable results due to protein flexibility. Graham Richards' lab was one of the first groups to utilize "fuzzy" pattern recognition algorithms taken from the field of image processing to solve problems in protein modeling. Thus, descriptor "fuzziness" was partly able to emulate conformational flexibility of the target while simultaneously enhancing the speed of the search. In this work, we extend these developments to a ligand-based method for describing and aligning molecules in flexible chemical space termed FEature POint PharmacophoreS (FEPOPS), which allows exploration of dynamic biological space. We develop a novel, combinatorial algorithm for molecular comparisons and evaluate it using the WOMBAT dataset. The new approach shows superior retrospective virtual screening performance than earlier shape-based or charge-based algorithms. Additionally, we use target prediction to evaluate how FEPOPS alignments match the molecules biological activity by identifying the atoms and features that make the key contributions to overall chemical similarity. Overall, we find that FEPOPS are sufficiently fuzzy and flexible to find not only new ligand scaffolds, but also challenging molecules that occupy different conformational states of dynamic biological space as from induced fits.

  5. Fast human pose estimation using 3D Zernike descriptors

    NASA Astrophysics Data System (ADS)

    Berjón, Daniel; Morán, Francisco

    2012-03-01

    Markerless video-based human pose estimation algorithms face a high-dimensional problem that is frequently broken down into several lower-dimensional ones by estimating the pose of each limb separately. However, in order to do so they need to reliably locate the torso, for which they typically rely on time coherence and tracking algorithms. Their losing track usually results in catastrophic failure of the process, requiring human intervention and thus precluding their usage in real-time applications. We propose a very fast rough pose estimation scheme based on global shape descriptors built on 3D Zernike moments. Using an articulated model that we configure in many poses, a large database of descriptor/pose pairs can be computed off-line. Thus, the only steps that must be done on-line are the extraction of the descriptors for each input volume and a search against the database to get the most likely poses. While the result of such process is not a fine pose estimation, it can be useful to help more sophisticated algorithms to regain track or make more educated guesses when creating new particles in particle-filter-based tracking schemes. We have achieved a performance of about ten fps on a single computer using a database of about one million entries.

  6. Derivatives in discrete mathematics: a novel graph-theoretical invariant for generating new 2/3D molecular descriptors. I. Theory and QSPR application.

    PubMed

    Marrero-Ponce, Yovani; Santiago, Oscar Martínez; López, Yoan Martínez; Barigye, Stephen J; Torrens, Francisco

    2012-11-01

    In this report, we present a new mathematical approach for describing chemical structures of organic molecules at atomic-molecular level, proposing for the first time the use of the concept of the derivative ([Formula: see text]) of a molecular graph (MG) with respect to a given event (E), to obtain a new family of molecular descriptors (MDs). With this purpose, a new matrix representation of the MG, which generalizes graph's theory's traditional incidence matrix, is introduced. This matrix, denominated the generalized incidence matrix, Q, arises from the Boolean representation of molecular sub-graphs that participate in the formation of the graph molecular skeleton MG and could be complete (representing all possible connected sub-graphs) or constitute sub-graphs of determined orders or types as well as a combination of these. The Q matrix is a non-quadratic and unsymmetrical in nature, its columns (n) and rows (m) are conditions (letters) and collection of conditions (words) with which the event occurs. This non-quadratic and unsymmetrical matrix is transformed, by algebraic manipulation, to a quadratic and symmetric matrix known as relations frequency matrix, F, which characterizes the participation intensity of the conditions (letters) in the events (words). With F, we calculate the derivative over a pair of atomic nuclei. The local index for the atomic nuclei i, Δ(i), can therefore be obtained as a linear combination of all the pair derivatives of the atomic nuclei i with all the rest of the j's atomic nuclei. Here, we also define new strategies that generalize the present form of obtaining global or local (group or atom-type) invariants from atomic contributions (local vertex invariants, LOVIs). In respect to this, metric (norms), means and statistical invariants are introduced. These invariants are applied to a vector whose components are the values Δ(i) for the atomic nuclei of the molecule or its fragments. Moreover, with the purpose of differentiating

  7. TDSIFT: a new descriptor for 2D and 3D ear recognition

    NASA Astrophysics Data System (ADS)

    Chen, Long; Mu, Zhichun; Nan, Bingfei; Zhang, Yi; Yang, Ruyin

    2017-02-01

    Descriptor is the key of any image-based recognition algorithm. For ear recognition, conventional descriptors are either based on 2D data or 3D data. 2D images provide rich texture information and human ear is a 3D surface that could offer shape information. It also inspires us that 2D data is more robust against occlusion while 3D data shows more robustness against illumination variation and pose variation. In this paper, we introduce a novel Texture and Depth Scale Invariant Feature Transform (TDSIFT) descriptor to encode 2D and 3D local features for ear recognition. Compared to the original Scale Invariant Feature Transform (SIFT) descriptor, the proposed TDSIFT shows its superiority by fusing 2D local information and 3D local information. Firstly, keypoints are detected and described on texture images. Then, 3D information of the keypoints located on the corresponding depth images is added to form the TDSIFT descriptor. Finally, a local feature based classification algorithm is adopted to identify ear samples by TDSIFT. Experimental results on a benchmark dataset demonstrate the feasibility and effectiveness of our proposed descriptor. The rank-1 recognition rate achieved on a gallery of 415 persons is 95.9% and the time involved in the computation is satisfactory compared to state-of-the-art methods.

  8. 3D Face Recognition Based on Multiple Keypoint Descriptors and Sparse Representation

    PubMed Central

    Zhang, Lin; Ding, Zhixuan; Li, Hongyu; Shen, Ying; Lu, Jianwei

    2014-01-01

    Recent years have witnessed a growing interest in developing methods for 3D face recognition. However, 3D scans often suffer from the problems of missing parts, large facial expressions, and occlusions. To be useful in real-world applications, a 3D face recognition approach should be able to handle these challenges. In this paper, we propose a novel general approach to deal with the 3D face recognition problem by making use of multiple keypoint descriptors (MKD) and the sparse representation-based classification (SRC). We call the proposed method 3DMKDSRC for short. Specifically, with 3DMKDSRC, each 3D face scan is represented as a set of descriptor vectors extracted from keypoints by meshSIFT. Descriptor vectors of gallery samples form the gallery dictionary. Given a probe 3D face scan, its descriptors are extracted at first and then its identity can be determined by using a multitask SRC. The proposed 3DMKDSRC approach does not require the pre-alignment between two face scans and is quite robust to the problems of missing data, occlusions and expressions. Its superiority over the other leading 3D face recognition schemes has been corroborated by extensive experiments conducted on three benchmark databases, Bosphorus, GavabDB, and FRGC2.0. The Matlab source code for 3DMKDSRC and the related evaluation results are publicly available at http://sse.tongji.edu.cn/linzhang/3dmkdsrcface/3dmkdsrc.htm. PMID:24940876

  9. 3D face recognition based on multiple keypoint descriptors and sparse representation.

    PubMed

    Zhang, Lin; Ding, Zhixuan; Li, Hongyu; Shen, Ying; Lu, Jianwei

    2014-01-01

    Recent years have witnessed a growing interest in developing methods for 3D face recognition. However, 3D scans often suffer from the problems of missing parts, large facial expressions, and occlusions. To be useful in real-world applications, a 3D face recognition approach should be able to handle these challenges. In this paper, we propose a novel general approach to deal with the 3D face recognition problem by making use of multiple keypoint descriptors (MKD) and the sparse representation-based classification (SRC). We call the proposed method 3DMKDSRC for short. Specifically, with 3DMKDSRC, each 3D face scan is represented as a set of descriptor vectors extracted from keypoints by meshSIFT. Descriptor vectors of gallery samples form the gallery dictionary. Given a probe 3D face scan, its descriptors are extracted at first and then its identity can be determined by using a multitask SRC. The proposed 3DMKDSRC approach does not require the pre-alignment between two face scans and is quite robust to the problems of missing data, occlusions and expressions. Its superiority over the other leading 3D face recognition schemes has been corroborated by extensive experiments conducted on three benchmark databases, Bosphorus, GavabDB, and FRGC2.0. The Matlab source code for 3DMKDSRC and the related evaluation results are publicly available at http://sse.tongji.edu.cn/linzhang/3dmkdsrcface/3dmkdsrc.htm.

  10. Novel TOPP descriptors in 3D-QSAR analysis of apoptosis inducing 4-aryl-4H-chromenes: comparison versus other 2D- and 3D-descriptors.

    PubMed

    Sciabola, Simone; Carosati, Emanuele; Cucurull-Sanchez, Lourdes; Baroni, Massimo; Mannhold, Raimund

    2007-10-01

    Novel 3D-descriptors using Triplets Of Pharmacophoric Points (TOPP) were evaluated in QSAR-studies on 80 apoptosis-inducing 4-aryl-4H-chromenes. A predictive QSAR model was obtained using PLS, confirmed by means of internal and external validations. Performance of the TOPP approach was compared with that of other 2D- and 3D-descriptors; statistical analysis indicates that TOPP descriptors perform best. A ranking of TOPP>GRIND>BCI 4096=ECFP>FCFP>GRID-GOLPE>DRAGON>MDL 166 was achieved. Finally, in a 'consensus' analysis predictions obtained using the single methods were compared with an average approach using six out of eight methods. The use of the average is statistically superior to the single methods. Beyond it, the use of several methods can help to easily investigate the presence/absence of outliers according to the 'consensus' of the predicted values: agreement among all the methods indicates a precise prediction, whereas large differences between predicted values (for the same compounds by different methods) would demand caution when using such predictions.

  11. Analyzing the relevance of shape descriptors in automated recognition of facial gestures in 3D images

    NASA Astrophysics Data System (ADS)

    Rodriguez A., Julian S.; Prieto, Flavio

    2013-03-01

    The present document shows and explains the results from analyzing shape descriptors (DESIRE and Spherical Spin Image) for facial recognition of 3D images. DESIRE is a descriptor made of depth images, silhouettes and rays extended from a polygonal mesh; whereas the Spherical Spin Image (SSI) associated to a polygonal mesh point, is a 2D histogram built from neighboring points by using the position information that captures features of the local shape. The database used contains images of facial expressions which in average were recognized 88.16% using a neuronal network and 91.11% with a Bayesian classifier in the case of the first descriptor; in contrast, the second descriptor only recognizes in average 32% and 23,6% using the same mentioned classifiers respectively.

  12. Comparison of 3D interest point detectors and descriptors for point cloud fusion

    NASA Astrophysics Data System (ADS)

    Hänsch, R.; Weber, T.; Hellwich, O.

    2014-08-01

    The extraction and description of keypoints as salient image parts has a long tradition within processing and analysis of 2D images. Nowadays, 3D data gains more and more importance. This paper discusses the benefits and limitations of keypoints for the task of fusing multiple 3D point clouds. For this goal, several combinations of 3D keypoint detectors and descriptors are tested. The experiments are based on 3D scenes with varying properties, including 3D scanner data as well as Kinect point clouds. The obtained results indicate that the specific method to extract and describe keypoints in 3D data has to be carefully chosen. In many cases the accuracy suffers from a too strong reduction of the available points to keypoints.

  13. Signature molecular descriptor : advanced applications.

    SciTech Connect

    Visco, Donald Patrick, Jr.

    2010-04-01

    In this work we report on the development of the Signature Molecular Descriptor (or Signature) for use in the solution of inverse design problems as well as in highthroughput screening applications. The ultimate goal of using Signature is to identify novel and non-intuitive chemical structures with optimal predicted properties for a given application. We demonstrate this in three studies: green solvent design, glucocorticoid receptor ligand design and the design of inhibitors for Factor XIa. In many areas of engineering, compounds are designed and/or modified in incremental ways which rely upon heuristics or institutional knowledge. Often multiple experiments are performed and the optimal compound is identified in this brute-force fashion. Perhaps a traditional chemical scaffold is identified and movement of a substituent group around a ring constitutes the whole of the design process. Also notably, a chemical being evaluated in one area might demonstrate properties very attractive in another area and serendipity was the mechanism for solution. In contrast to such approaches, computer-aided molecular design (CAMD) looks to encompass both experimental and heuristic-based knowledge into a strategy that will design a molecule on a computer to meet a given target. Depending on the algorithm employed, the molecule which is designed might be quite novel (re: no CAS registration number) and/or non-intuitive relative to what is known about the problem at hand. While CAMD is a fairly recent strategy (dating to the early 1980s), it contains a variety of bottlenecks and limitations which have prevented the technique from garnering more attention in the academic, governmental and industrial institutions. A main reason for this is how the molecules are described in the computer. This step can control how models are developed for the properties of interest on a given problem as well as how to go from an output of the algorithm to an actual chemical structure. This report

  14. ANN expert system screening for illicit amphetamines using molecular descriptors

    NASA Astrophysics Data System (ADS)

    Gosav, S.; Praisler, M.; Dorohoi, D. O.

    2007-05-01

    The goal of this study was to develop and an artificial neural network (ANN) based on computed descriptors, which would be able to classify the molecular structures of potential illicit amphetamines and to derive their biological activity according to the similarity of their molecular structure with amphetamines of known toxicity. The system is necessary for testing new molecular structures for epidemiological, clinical, and forensic purposes. It was built using a database formed by 146 compounds representing drugs of abuse (mainly central stimulants, hallucinogens, sympathomimetic amines, narcotics and other potent analgesics), precursors, or derivatized counterparts. Their molecular structures were characterized by computing three types of descriptors: 38 constitutional descriptors (CDs), 69 topological descriptors (TDs) and 160 3D-MoRSE descriptors (3DDs). An ANN system was built for each category of variables. All three networks (CD-NN, TD-NN and 3DD-NN) were trained to distinguish between stimulant amphetamines, hallucinogenic amphetamines, and nonamphetamines. A selection of variables was performed when necessary. The efficiency with which each network identifies the class identity of an unknown sample was evaluated by calculating several figures of merit. The results of the comparative analysis are presented.

  15. An Effective 3D Shape Descriptor for Object Recognition with RGB-D Sensors

    PubMed Central

    Liu, Zhong; Zhao, Changchen; Wu, Xingming; Chen, Weihai

    2017-01-01

    RGB-D sensors have been widely used in various areas of computer vision and graphics. A good descriptor will effectively improve the performance of operation. This article further analyzes the recognition performance of shape features extracted from multi-modality source data using RGB-D sensors. A hybrid shape descriptor is proposed as a representation of objects for recognition. We first extracted five 2D shape features from contour-based images and five 3D shape features over point cloud data to capture the global and local shape characteristics of an object. The recognition performance was tested for category recognition and instance recognition. Experimental results show that the proposed shape descriptor outperforms several common global-to-global shape descriptors and is comparable to some partial-to-global shape descriptors that achieved the best accuracies in category and instance recognition. Contribution of partial features and computational complexity were also analyzed. The results indicate that the proposed shape features are strong cues for object recognition and can be combined with other features to boost accuracy. PMID:28245553

  16. Teaching Molecular 3-D Literacy

    ERIC Educational Resources Information Center

    Richardson, David C.; Richardson, Jane S.

    2002-01-01

    This article describes how the use of interactive molecular graphics makes a unique and important contribution to student learning of biochemistry and molecular biology at any level. These authors developed the concept of the kinemage (from "kinetic image"), a different way of organizing computer graphics that is aimed explicitly at the…

  17. 3D Printing of Molecular Models

    ERIC Educational Resources Information Center

    Gardner, Adam; Olson, Arthur

    2016-01-01

    Physical molecular models have played a valuable role in our understanding of the invisible nano-scale world. We discuss 3D printing and its use in producing models of the molecules of life. Complex biomolecular models, produced from 3D printed parts, can demonstrate characteristics of molecular structure and function, such as viral self-assembly,…

  18. Beyond Rotatable Bond Counts: Capturing 3D Conformational Flexibility in a Single Descriptor

    PubMed Central

    2016-01-01

    A new molecular descriptor, nConf20, based on chemical connectivity, is presented which captures the accessible conformational space of a molecule. Currently the best available two-dimensional descriptors for quantifying the flexibility of a particular molecule are the rotatable bond count (RBC) and the Kier flexibility index. We present a descriptor which captures this information by sampling the conformational space of a molecule using the RDKit conformer generator. Flexibility has previously been identified as a key feature in determining whether a molecule is likely to crystallize or not. For this application, nConf20 significantly outperforms previously reported single-variable classifiers and also assists rule-based analysis of black-box machine learning classification algorithms. PMID:28024401

  19. Beyond Rotatable Bond Counts: Capturing 3D Conformational Flexibility in a Single Descriptor.

    PubMed

    Wicker, Jerome G P; Cooper, Richard I

    2016-12-27

    A new molecular descriptor, nConf20, based on chemical connectivity, is presented which captures the accessible conformational space of a molecule. Currently the best available two-dimensional descriptors for quantifying the flexibility of a particular molecule are the rotatable bond count (RBC) and the Kier flexibility index. We present a descriptor which captures this information by sampling the conformational space of a molecule using the RDKit conformer generator. Flexibility has previously been identified as a key feature in determining whether a molecule is likely to crystallize or not. For this application, nConf20 significantly outperforms previously reported single-variable classifiers and also assists rule-based analysis of black-box machine learning classification algorithms.

  20. Novel 3D bio-macromolecular bilinear descriptors for protein science: Predicting protein structural classes.

    PubMed

    Marrero-Ponce, Yovani; Contreras-Torres, Ernesto; García-Jacas, César R; Barigye, Stephen J; Cubillán, Néstor; Alvarado, Ysaías J

    2015-06-07

    In the present study, we introduce novel 3D protein descriptors based on the bilinear algebraic form in the ℝ(n) space on the coulombic matrix. For the calculation of these descriptors, macromolecular vectors belonging to ℝ(n) space, whose components represent certain amino acid side-chain properties, were used as weighting schemes. Generalization approaches for the calculation of inter-amino acidic residue spatial distances based on Minkowski metrics are proposed. The simple- and double-stochastic schemes were defined as approaches to normalize the coulombic matrix. The local-fragment indices for both amino acid-types and amino acid-groups are presented in order to permit characterizing fragments of interest in proteins. On the other hand, with the objective of taking into account specific interactions among amino acids in global or local indices, geometric and topological cut-offs are defined. To assess the utility of global and local indices a classification model for the prediction of the major four protein structural classes, was built with the Linear Discriminant Analysis (LDA) technique. The developed LDA-model correctly classifies the 92.6% and 92.7% of the proteins on the training and test sets, respectively. The obtained model showed high values of the generalized square correlation coefficient (GC(2)) on both the training and test series. The statistical parameters derived from the internal and external validation procedures demonstrate the robustness, stability and the high predictive power of the proposed model. The performance of the LDA-model demonstrates the capability of the proposed indices not only to codify relevant biochemical information related to the structural classes of proteins, but also to yield suitable interpretability. It is anticipated that the current method will benefit the prediction of other protein attributes or functions.

  1. Reverse engineering chemical structures from molecular descriptors : how many solutions?

    SciTech Connect

    Brown, William Michael; Martin, Shawn Bryan; Faulon, Jean-Loup Michel

    2005-06-01

    Physical, chemical and biological properties are the ultimate information of interest for chemical compounds. Molecular descriptors that map structural information to activities and properties are obvious candidates for information sharing. In this paper, we consider the feasibility of using molecular descriptors to safely exchange chemical information in such a way that the original chemical structures cannot be reverse engineered. To investigate the safety of sharing such descriptors, we compute the degeneracy (the number of structure matching a descriptor value) of several 2D descriptors, and use various methods to search for and reverse engineer structures. We examine degeneracy in the entire chemical space taking descriptors values from the alkane isomer series and the PubChem database. We further use a stochastic search to retrieve structures matching specific topological index values. Finally, we investigate the safety of exchanging of fragmental descriptors using deterministic enumeration.

  2. Application of 3D Zernike descriptors to shape-based ligand similarity searching

    PubMed Central

    2009-01-01

    Background The identification of promising drug leads from a large database of compounds is an important step in the preliminary stages of drug design. Although shape is known to play a key role in the molecular recognition process, its application to virtual screening poses significant hurdles both in terms of the encoding scheme and speed. Results In this study, we have examined the efficacy of the alignment independent three-dimensional Zernike descriptor (3DZD) for fast shape based similarity searching. Performance of this approach was compared with several other methods including the statistical moments based ultrafast shape recognition scheme (USR) and SIMCOMP, a graph matching algorithm that compares atom environments. Three benchmark datasets are used to thoroughly test the methods in terms of their ability for molecular classification, retrieval rate, and performance under the situation that simulates actual virtual screening tasks over a large pharmaceutical database. The 3DZD performed better than or comparable to the other methods examined, depending on the datasets and evaluation metrics used. Reasons for the success and the failure of the shape based methods for specific cases are investigated. Based on the results for the three datasets, general conclusions are drawn with regard to their efficiency and applicability. Conclusion The 3DZD has unique ability for fast comparison of three-dimensional shape of compounds. Examples analyzed illustrate the advantages and the room for improvements for the 3DZD. PMID:20150998

  3. Investigation Of Integrating Three-Dimensional (3-D) Geometry Into The Visual Anatomical Injury Descriptor (Visual AID) Using WebGL

    DTIC Science & Technology

    2011-08-01

    into the Visual Anatomical Injury Descriptor (Visual AID) Using WebGL AUTUMN KULAGA MENTOR: PATRICK GILLICH WARFIGHTER SURVIVABILITY BRANCH...Investigation Of Integrating Three-Dimensional (3-D) Geometry Into The Visual Anatomical Injury Descriptor (Visual AID) Using WebGL 5a. CONTRACT...discusses the Web-based 3-D environment prototype being developed to understand the feasibility of integrating WebGL into Visual AID. Using WebGL will

  4. Analysing molecular polar surface descriptors to predict blood-brain barrier permeation.

    PubMed

    Shityakov, Sergey; Neuhaus, Winfried; Dandekar, Thomas; Förster, Carola

    2013-01-01

    Molecular polar surface (PS) descriptors are very useful parameters in prediction of drug transport properties. They could be also used to investigate the blood-brain barrier (BBB) permeation rate for various chemical compounds. In this study, a dataset of drugs (n = 19) from various pharmacological groups was studied to estimate their potential properties to permeate across the BBB. Experimental logBB data were available as steady-state distribution values of the in vivo rat model for these molecules. Including accurate calculation of the electrostatic potential maps, polar surface descriptors, such as a two-dimensional polar surface area (2D-PSA), topological polar surface area (TPSA) and three-dimensional polar surface area or polar area (3D-PSA; PA) were measured and analysed. We report the strong correlation of these descriptors with logBB values for the prediction of BBB permeation using the linear partial least squares (PLS) fitting technique. The 3D-PSA descriptor showed the best fit to logBB values with R² = 0.92 and RMSD = 0.29 (p-value < 0.0001). The obtained results demonstrate that all descriptors bear high predictive powers and could provide an efficient strategy to envisage the pharmacokinetic properties of chemical compounds to permeate across the BBB at an early stage of the drug development process.

  5. Molecular design and QSARs/QSPRs with molecular descriptors family.

    PubMed

    Bolboacă, Sorana D; Jäntschi, Lorentz; Diudea, Mircea V

    2013-06-01

    The aim of the present paper is to present the methodology of the molecular descriptors family (MDF) as an integrative tool in molecular modeling and its abilities as a multivariate QSAR/QSPR modeling tool. An algorithm for extracting useful information from the topological and geometrical representation of chemical compounds was developed and integrated to calculate MDF members. The MDF methodology was implemented and the software is available online (http://l.academicdirect.org/Chemistry/SARs/MDF_SARs/). This integrative tool was developed in order to maximize performance, functionality, efficiency and portability. The MDF methodology is able to provide reliable and valid multiple linear regression models. Furthermore, in many cases, the MDF models were better than the published results in the literature in terms of correlation coefficients (statistically significant Steiger's Z test at a significance level of 5%) and/or in terms of values of information criteria and Kubinyi function. The MDF methodology developed and implemented as a platform for investigating and characterizing quantitative relationships between the chemical structure and the activity/property of active compounds was used on more than 50 study cases. In almost all cases, the methodology allowed obtaining of QSAR/QSPR models improved in explanatory power of structure-activity and structure-property relationships. The algorithms applied in the computation of geometric and topological descriptors (useful in modeling physicochemical or biological properties of molecules) and those used in searching for reliable and valid multiple linear regression models certain enrich the pool of low-cost low-time drug design tools.

  6. Segmentation of Brain MRI Using SOM-FCM-Based Method and 3D Statistical Descriptors

    PubMed Central

    Ortiz, Andrés; Palacio, Antonio A.; Górriz, Juan M.; Ramírez, Javier; Salas-González, Diego

    2013-01-01

    Current medical imaging systems provide excellent spatial resolution, high tissue contrast, and up to 65535 intensity levels. Thus, image processing techniques which aim to exploit the information contained in the images are necessary for using these images in computer-aided diagnosis (CAD) systems. Image segmentation may be defined as the process of parcelling the image to delimit different neuroanatomical tissues present on the brain. In this paper we propose a segmentation technique using 3D statistical features extracted from the volume image. In addition, the presented method is based on unsupervised vector quantization and fuzzy clustering techniques and does not use any a priori information. The resulting fuzzy segmentation method addresses the problem of partial volume effect (PVE) and has been assessed using real brain images from the Internet Brain Image Repository (IBSR). PMID:23762192

  7. Correlation between calculated molecular descriptors of excipient amino acids and experimentally observed thermal stability of lysozyme.

    PubMed

    Meng-Lund, Helena; Friis, Natascha; van de Weert, Marco; Rantanen, Jukka; Poso, Antti; Grohganz, Holger; Jorgensen, Lene

    2017-03-21

    A quantitative structure-property relationship (QSPR) between protein stability and the physicochemical properties of excipients was investigated to enable a more rational choice of stabilizing excipients than prior knowledge. The thermal transition temperature and aggregation time were determined for lysozyme in combination with 13 different amino acids using high throughput fluorescence spectroscopy and kinetic static light scattering measurements. On the theoretical side, around 200 2D and 3D molecular descriptors were calculated based on the amino acids' chemical structure. Multivariate data analysis was applied to correlate the descriptors with the experimental results. It was possible to identify descriptors, i.e. amino acids properties, with a positive influence on either transition temperature or aggregation onset time, or both. A high number of hydrogen bond acceptor moieties was the most prominent stabilizing factor for both responses, whereas hydrophilic surface properties and high molecular mass density mostly had a positive influence on the unfolding temperature. A high partition coefficient (logP(o/w)) was identified as the most prominent destabilizing factor for both responses. The QSPR shows good correlation between calculated molecular descriptors and the measured stabilizing effect of amino acids on lysozyme.

  8. CH5M3D: an HTML5 program for creating 3D molecular structures

    PubMed Central

    2013-01-01

    Background While a number of programs and web-based applications are available for the interactive display of 3-dimensional molecular structures, few of these provide the ability to edit these structures. For this reason, we have developed a library written in JavaScript to allow for the simple creation of web-based applications that should run on any browser capable of rendering HTML5 web pages. While our primary interest in developing this application was for educational use, it may also prove useful to researchers who want a light-weight application for viewing and editing small molecular structures. Results Molecular compounds are drawn on the HTML5 Canvas element, with the JavaScript code making use of standard techniques to allow display of three-dimensional structures on a two-dimensional canvas. Information about the structure (bond lengths, bond angles, and dihedral angles) can be obtained using a mouse or other pointing device. Both atoms and bonds can be added or deleted, and rotation about bonds is allowed. Routines are provided to read structures either from the web server or from the user’s computer, and creation of galleries of structures can be accomplished with only a few lines of code. Documentation and examples are provided to demonstrate how users can access all of the molecular information for creation of web pages with more advanced features. Conclusions A light-weight (≈ 75 kb) JavaScript library has been made available that allows for the simple creation of web pages containing interactive 3-dimensional molecular structures. Although this library is designed to create web pages, a web server is not required. Installation on a web server is straightforward and does not require any server-side modules or special permissions. The ch5m3d.js library has been released under the GNU GPL version 3 open-source license and is available from http://sourceforge.net/projects/ch5m3d/. PMID:24246004

  9. Molecular cartography of the human skin surface in 3D.

    PubMed

    Bouslimani, Amina; Porto, Carla; Rath, Christopher M; Wang, Mingxun; Guo, Yurong; Gonzalez, Antonio; Berg-Lyon, Donna; Ackermann, Gail; Moeller Christensen, Gitte Julie; Nakatsuji, Teruaki; Zhang, Lingjuan; Borkowski, Andrew W; Meehan, Michael J; Dorrestein, Kathleen; Gallo, Richard L; Bandeira, Nuno; Knight, Rob; Alexandrov, Theodore; Dorrestein, Pieter C

    2015-04-28

    The human skin is an organ with a surface area of 1.5-2 m(2) that provides our interface with the environment. The molecular composition of this organ is derived from host cells, microbiota, and external molecules. The chemical makeup of the skin surface is largely undefined. Here we advance the technologies needed to explore the topographical distribution of skin molecules, using 3D mapping of mass spectrometry data and microbial 16S rRNA amplicon sequences. Our 3D maps reveal that the molecular composition of skin has diverse distributions and that the composition is defined not only by skin cells and microbes but also by our daily routines, including the application of hygiene products. The technological development of these maps lays a foundation for studying the spatial relationships of human skin with hygiene, the microbiota, and environment, with potential for developing predictive models of skin phenotypes tailored to individual health.

  10. Molecular cartography of the human skin surface in 3D

    PubMed Central

    Bouslimani, Amina; Porto, Carla; Rath, Christopher M.; Wang, Mingxun; Guo, Yurong; Gonzalez, Antonio; Berg-Lyon, Donna; Ackermann, Gail; Moeller Christensen, Gitte Julie; Nakatsuji, Teruaki; Zhang, Lingjuan; Borkowski, Andrew W.; Meehan, Michael J.; Dorrestein, Kathleen; Gallo, Richard L.; Bandeira, Nuno; Knight, Rob; Alexandrov, Theodore; Dorrestein, Pieter C.

    2015-01-01

    The human skin is an organ with a surface area of 1.5–2 m2 that provides our interface with the environment. The molecular composition of this organ is derived from host cells, microbiota, and external molecules. The chemical makeup of the skin surface is largely undefined. Here we advance the technologies needed to explore the topographical distribution of skin molecules, using 3D mapping of mass spectrometry data and microbial 16S rRNA amplicon sequences. Our 3D maps reveal that the molecular composition of skin has diverse distributions and that the composition is defined not only by skin cells and microbes but also by our daily routines, including the application of hygiene products. The technological development of these maps lays a foundation for studying the spatial relationships of human skin with hygiene, the microbiota, and environment, with potential for developing predictive models of skin phenotypes tailored to individual health. PMID:25825778

  11. New molecular descriptors based on local properties at the molecular surface and a boiling-point model derived from them.

    PubMed

    Ehresmann, Bernd; de Groot, Marcel J; Alex, Alexander; Clark, Timothy

    2004-01-01

    New molecular descriptors based on statistical descriptions of the local ionization potential, local electron affinity, and the local polarizability at the surface of the molecule are proposed. The significance of these descriptors has been tested by calculating them for the Maybridge database in addition to our set of 26 descriptors reported previously. The new descriptors show little correlation with those already in use. Furthermore, the principal components of the extended set of descriptors for the Maybridge data show that especially the descriptors based on the local electron affinity extend the variance in our set of descriptors, which we have previously shown to be relevant to physical properties. The first nine principal components are shown to be most significant. As an example of the usefulness of the new descriptors, we have set up a QSPR model for boiling points using both the old and new descriptors.

  12. Molecular Predictors of 3D Morphogenesis by Breast Cancer Cell Lines in 3D Culture

    SciTech Connect

    Han, Ju; Chang, Hang; Giricz, Orsi; Lee, Genee; Baehner, Frederick; Gray, Joe; Bissell, Mina; Kenny, Paraic; Parvin, Bahram

    2010-02-01

    Correlative analysis of molecular markers with phenotypic signatures is the simplest model for hypothesis generation. In this paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy, and computational methods were developed to segment and represent each colony at multiple dimensions. Subsequently, subpopulations from these morphological responses were identified through consensus clustering to reveal three clusters of round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypes clustered together (e.g., ERBB2 amplified cell lines sharing the same morphometric properties as the grape-like phenotype). Next, associations with molecular features were realized through (i) differential analysis within each morphological cluster, and (ii) regression analysis across the entire panel of cell lines. In both cases, the dominant genes that are predictive of the morphological signatures were identified. Specifically, PPAR? has been associated with the invasive stellate morphological phenotype, which corresponds to triple-negative pathobiology. PPAR? has been validated through two supporting biological assays.

  13. [A new SVRDF 3D-descriptor of amino acids and its application to peptide quantitative structure activity relationship].

    PubMed

    Tong, Jian-Bo; Zhang, Sheng-Wan; Cheng, Su-Li; Li, Gai-Xian

    2007-01-01

    To establish a new amino acid structure descriptor that can be applied to polypeptide quantitative structure activity relationship (QSAR) studies, a new descriptor, SVRDF, was derived from a principal components analysis of a matrix of 150 radial distribution function index of amino acids. The scale was then applied in three panels of peptide QSAR that were molded by partial least squares regression. The obtained models with the correlation coefficients (R2(cum)), cross-validation correlation coefficients (Q2(cum)) were 0.766 and 0.724 for 48 bitter tasting dipeptides; 0.941 and 0.811 for 21 oxytocin analogues; 0.996 and 0.919 for 20 thromboplastin inhibitors. Satisfactory results showed that information related to biological activity can be systemically expressed by SVRDF scales, which may be an useful structural expression methodology for the study of peptides QSAR.

  14. 3D metamaterial absorber for attomole molecular detection (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Tanaka, Takuo; Ishikawa, Atsushi

    2016-09-01

    3D Metamaterial absorber was used for a background-suppressed surface-enhanced molecular detection technique. By utilizing the resonant coupling of plasmonic modes of a metamaterial absorber and infrared (IR) vibrational modes of a self-assembled monolayer (SAM), attomole level molecular sensitivity was experimentally demonstrated. IR absorption spectroscopy of molecular vibrations is of importance in chemical, material, medical science and so on, since it provides essential information of the molecular structure, composition, and orientation. In the vibrational spectroscopic techniques, in addition to the weak signals from the molecules, strong background degrades the signal-to-noise ratio, and suppression of the background is crucial for the further improvement of the sensitivity. Here, we demonstrate low-background resonant Surface enhanced IR absorption (SEIRA) by using the metamaterial IR absorber that offers significant background suppression as well as plasmonic enhancement. The fabricated metamaterial consisted of 1D array of Au micro-ribbons on a thick Au film separated by a transparent gap layer made of MgF2. The surface structures were designed to exhibit an anomalous IR absorption at 3000 cm-1, which spectrally overlapped with C-H stretching vibrational modes. 16-Mercaptohexadecanoic acid (16-MHDA) was used as a test molecule, which formed a 2-nm thick SAM with their thiol head-group chemisorbed on the Au surface. In the FTIR measurements, the symmetric and asymmetric C-H stretching modes were clearly observed as reflection peaks within a broad plasmonic absorption of the metamaterial.

  15. Prediction of pesticides chromatographic lipophilicity from the computational molecular descriptors.

    PubMed

    Casoni, Dorina; Petre, Jana; David, Victor; Sârbu, Costel

    2011-02-01

    Quantitative structure-property relationship models were developed for the prediction of pesticides and some PAH compounds lipophilicity based on a wide set of computational molecular descriptors and a set of experimental chromatographic data. The chromatographic lipophilicity of pesticides has been evaluated by high-performance liquid chromatography (HPLC) using different chemically bonded (C18, C8, CN and Phenyl HPLC columns) stationary phases and two different organic modifiers (methanol and acetonitrile, respectively) in the mobile phase composition. Through a systematic study, by using the classic multivariate analysis, several quantitative structure-property/lipophilicity multi-dimensional models were established. Multiple linear regression and genetic algorithm for the variable subset selection were used. The internal and external statistical evaluation procedures revealed some appropriate models for the chromatographic lipophilicity prediction of pesticides. Moreover, the statistical parameters of regression and those obtained by applying t-test for the intercept (a(0)) and for the slope (a(1)) in order to evaluate relationship between experimental and predicted octanol-water partition coefficients in case of the test set compounds, revealed two statistically valid models that can be successfully used in lipophilicity prediction of pesticides.

  16. A rotation-translation invariant molecular descriptor of partial charges and its use in ligand-based virtual screening

    PubMed Central

    2014-01-01

    Background Measures of similarity for chemical molecules have been developed since the dawn of chemoinformatics. Molecular similarity has been measured by a variety of methods including molecular descriptor based similarity, common molecular fragments, graph matching and 3D methods such as shape matching. Similarity measures are widespread in practice and have proven to be useful in drug discovery. Because of our interest in electrostatics and high throughput ligand-based virtual screening, we sought to exploit the information contained in atomic coordinates and partial charges of a molecule. Results A new molecular descriptor based on partial charges is proposed. It uses the autocorrelation function and linear binning to encode all atoms of a molecule into two rotation-translation invariant vectors. Combined with a scoring function, the descriptor allows to rank-order a database of compounds versus a query molecule. The proposed implementation is called ACPC (AutoCorrelation of Partial Charges) and released in open source. Extensive retrospective ligand-based virtual screening experiments were performed and other methods were compared with in order to validate the method and associated protocol. Conclusions While it is a simple method, it performed remarkably well in experiments. At an average speed of 1649 molecules per second, it reached an average median area under the curve of 0.81 on 40 different targets; hence validating the proposed protocol and implementation. PMID:24887178

  17. Local plate/rod descriptors of 3D trabecular bone micro-CT images from medial axis topologic analysis

    SciTech Connect

    Peyrin, Francoise; Attali, Dominique; Chappard, Christine; Benhamou, Claude Laurent

    2010-08-15

    Purpose: Trabecular bone microarchitecture is made of a complex network of plate and rod structures evolving with age and disease. The purpose of this article is to propose a new 3D local analysis method for the quantitative assessment of parameters related to the geometry of trabecular bone microarchitecture. Methods: The method is based on the topologic classification of the medial axis of the 3D image into branches, rods, and plates. Thanks to the reversibility of the medial axis, the classification is next extended to the whole 3D image. Finally, the percentages of rods and plates as well as their mean thicknesses are calculated. The method was applied both to simulated test images and 3D micro-CT images of human trabecular bone. Results: The classification of simulated phantoms made of plates and rods shows that the maximum error in the quantitative percentages of plate and rods is less than 6% and smaller than with the structure model index (SMI). Micro-CT images of human femoral bone taken in osteoporosis and early or advanced osteoarthritis were analyzed. Despite the large physiological variability, the present method avoids the underestimation of rods observed with other local methods. The relative percentages of rods and plates were not significantly different between osteoarthritis and osteoporotic groups, whereas their absolute percentages were in relation to an increase of rod and plate thicknesses in advanced osteoarthritis with also higher relative and absolute number of nodes. Conclusions: The proposed method is model-independent, robust to surface irregularities, and enables geometrical characterization of not only skeletal structures but entire 3D images. Its application provided more accurate results than the standard SMI on simple simulated phantoms, but the discrepancy observed on the advanced osteoarthritis group raises questions that will require further investigations. The systematic use of such a local method in the characterization of

  18. A 3D visualization system for molecular structures

    NASA Technical Reports Server (NTRS)

    Green, Terry J.

    1989-01-01

    The properties of molecules derive in part from their structures. Because of the importance of understanding molecular structures various methodologies, ranging from first principles to empirical technique, were developed for computing the structure of molecules. For large molecules such as polymer model compounds, the structural information is difficult to comprehend by examining tabulated data. Therefore, a molecular graphics display system, called MOLDS, was developed to help interpret the data. MOLDS is a menu-driven program developed to run on the LADC SNS computer systems. This program can read a data file generated by the modeling programs or data can be entered using the keyboard. MOLDS has the following capabilities: draws the 3-D representation of a molecule using stick, ball and ball, or space filled model from Cartesian coordinates, draws different perspective views of the molecule; rotates the molecule on the X, Y, Z axis or about some arbitrary line in space, zooms in on a small area of the molecule in order to obtain a better view of a specific region; and makes hard copy representation of molecules on a graphic printer. In addition, MOLDS can be easily updated and readily adapted to run on most computer systems.

  19. Collision cross section prediction of deprotonated phenolics in a travelling-wave ion mobility spectrometer using molecular descriptors and chemometrics.

    PubMed

    Gonzales, Gerard Bryan; Smagghe, Guy; Coelus, Sofie; Adriaenssens, Dieter; De Winter, Karel; Desmet, Tom; Raes, Katleen; Van Camp, John

    2016-06-14

    The combination of ion mobility and mass spectrometry (MS) affords significant improvements over conventional MS/MS, especially in the characterization of isomeric metabolites due to the differences in their collision cross sections (CCS). Experimentally obtained CCS values are typically matched with theoretical CCS values from Trajectory Method (TM) and/or Projection Approximation (PA) calculations. In this paper, predictive models for CCS of deprotonated phenolics were developed using molecular descriptors and chemometric tools, stepwise multiple linear regression (SMLR), principal components regression (PCR), and partial least squares regression (PLS). A total of 102 molecular descriptors were generated and reduced to 28 after employing a feature selection tool, composed of mass, topological descriptors, Jurs descriptors and shadow indices. Therefore, the generated models considered the effects of mass, 3D conformation and partial charge distribution on CCS, which are the main parameters for either TM or PA (only 3D conformation) calculations. All three techniques yielded highly predictive models for both the training (R(2)SMLR = 0.9911; R(2)PCR = 0.9917; R(2)PLS = 0.9918) and validation datasets (R(2)SMLR = 0.9489; R(2)PCR = 0.9761; R(2)PLS = 0.9760). Also, the high cross validated R(2) values indicate that the generated models are robust and highly predictive (Q(2)SMLR = 0.9859; Q(2)PCR = 0.9748; Q(2)PLS = 0.9760). The predictions were also very comparable to the results from TM calculations using modified mobcal (N2). Most importantly, this method offered a rapid (<10 min) alternative to TM calculations without compromising predictive ability. These methods could therefore be used in routine analysis and could be easily integrated to metabolite identification platforms.

  20. Total and local (atom and atom type) molecular quadratic indices: significance interpretation, comparison to other molecular descriptors, and QSPR/QSAR applications.

    PubMed

    Ponce, Yovani Marrero

    2004-12-15

    This paper describes the significance interpretation, comparison to other molecular descriptors, and QSPR/QSAR applications of a new set of molecular descriptors: atom, atom type, and total molecular quadratic indices. The features of the kth total and local quadratic indices are illustrated by examples of various types of molecular structures, including chain lengthening, branching, heteroatoms content, and multiple bonds. The linear independence of the local (atom type) quadratic indices to others 0D, 1D, 2D, and 3D molecular descriptors is demonstrated by using principal component analysis for 42 heterogeneous molecules. It is concluded that the local quadratic indices are independent indices containing important structural information to be used in QSPR/QSAR and drug design studies. In this sense, molecular quadratic indices were used to the description and prediction of the boiling point of 28 alkyl alcohols and to the modeling of the partition coefficient (logP), specific rate constant (logk), and antibacterial activity of 2-furylethylene derivatives. These models were statistically significant and showed very good stability to data variation in leave-one-out (LOO) cross-validation experiment. The comparison with the other approaches also revealed good behaviors of our method in this QSAR study.

  1. [COMMODE] a large-scale database of molecular descriptors using compounds from PubChem

    PubMed Central

    2013-01-01

    Background Molecular descriptors have been extensively used in the field of structure-oriented drug design and structural chemistry. They have been applied in QSPR and QSAR models to predict ADME-Tox properties, which specify essential features for drugs. Molecular descriptors capture chemical and structural information, but investigating their interpretation and meaning remains very challenging. Results This paper introduces a large-scale database of molecular descriptors called COMMODE containing more than 25 million compounds originated from PubChem. About 2500 DRAGON-descriptors have been calculated for all compounds and integrated into this database, which is accessible through a web interface at http://commode.i-med.ac.at. PMID:24225386

  2. 3D Printing of Molecular Potential Energy Surface Models

    ERIC Educational Resources Information Center

    Lolur, Phalgun; Dawes, Richard

    2014-01-01

    Additive manufacturing, commonly known as 3D printing, is gaining popularity in a variety of applications and has recently become routinely available. Today, 3D printing services are not only found in engineering design labs and through online companies, but also in university libraries offering student access. In addition, affordable options for…

  3. 'Quasi-Mixture' Descriptors for QSPR Analysis of Molecular Macroscopic Properties. The Critical Properties of Organic Compounds.

    PubMed

    Mokshyna, E; Nedostup, V I; Polishchuk, P G; Kuzmin, V E

    2014-10-01

    Rational approach towards the QSAR/QSPR modeling requires the descriptors to be computationally efficient, yet physically and chemically meaningful. On the basis of existing simplex representation of molecular structure (SiRMS) the novel 'quasi-mixture' descriptors were developed in order to accomplish the goal of characterization molecules on 2D level (i.e. without explicit generation of 3D structure and exhaustive conformational search) with account for potential intermolecular interactions. The critical properties of organic compounds were chosen as target properties for the estimation of descriptors' efficacy because of their well-known physical nature, rigorously estimated experimental errors and large quantity of experimental data. Among described properties are critical temperature, pressure and volume. Obtained models have high statistical characteristics, therefore showing the efficacy of suggested 'quasi-mixture' approach. Moreover, 'quasi-mixture' approach, as a branch of the SiRMS, allows to interpret results in terms of simple basic molecular properties. The obtained picture of influences corresponds to the accepted theoretical views.

  4. Classification of some active compounds and their inactive analogues using two three-dimensional molecular descriptors derived from computation of three-dimensional convex hulls for structures theoretically generated for them.

    PubMed

    Lin, T H; Yu, Y S; Chen, H J

    2000-01-01

    Two three-dimensional (3D) molecular descriptors are used to classify 73 protease inhibitors against the human immunodeficiency virus type 1 (HIV-1). X-ray structures of these HIV-1 protease bound inhibitors are used as templates to generate the most probable bioactive conformations of the inhibitors. A convex hull computation algorithm is applied to each structure generated. The frequency of atoms lying on the vertexes of each hull is counted. Vertexes of the same atomic charge state are then gathered together as a set of commonly exposed groups for all the structures generated. The first 3D descriptor is computed as the maximum molecular path length among any three distinct commonly exposed groups, while the second 3D one is computed as the maximum molecular path length among any three atoms of nonconvex hull vertexes. We find that the 73 HIV-1 protease inhibitors can be classified by the first 3D descriptor into two groups, which agrees with the result of visual classification using the activity data as a criterion for these compounds. The classification scheme is then used to classify a database of 427 active trypsin inhibitors and their inactive analogues. The structures of these compounds are generated theoretically from steps of energy minimization and molecular dynamics. Classification for all these compounds is performed using the SYBYL hierarchical clustering method on the first 3D descriptor and then the second 3D one computed. It is found that some inactive analogues are completely separated from the active inhibitors at the first stage of classification using the first 3D descriptor. Most of the highly active inhibitors are classified into a cluster at the second stage of classification using the second 3D descriptor. Finally, most of these highly active inhibitors are separated from all the accompanying inactive analogues in the cluster through a structural alignment process using a set of commonly exposed groups determined for them.

  5. Understanding the comparative molecular field analysis (CoMFA) in terms of molecular quantum similarity and DFT-based reactivity descriptors.

    PubMed

    Morales-Bayuelo, Alejandro; Matute, Ricardo A; Caballero, Julio

    2015-06-01

    The three-dimensional quantitative structure-activity relationship (3D QSAR) models have many applications, although the inherent complexity to understand the results coming from 3D-QSAR arises the necessity of new insights in the interpretation of them. Hence, the quantum similarity field as well as reactivity descriptors based on the density functional theory were used in this work as a consistent approach to better understand the 3D-QSAR studies in drug design. For this purpose, the quantification of steric and electrostatic effects on a series of bicycle [4.1.0] heptane derivatives as melanin-concentrating hormone receptor 1 antagonists were performed on the basis of molecular quantum similarity measures. The maximum similarity superposition and the topo-geometrical superposition algorithms were used as molecular alignment methods to deal with the problem of relative molecular orientation in quantum similarity. In addition, a chemical reactivity analysis using global and local descriptors such as chemical hardness, softness, electrophilicity, and Fukui functions, was developed. Overall, our results suggest that the application of this methodology in drug design can be useful when the receptor is known or even unknown.

  6. A new graph-based molecular descriptor using the canonical representation of the molecule.

    PubMed

    Hentabli, Hamza; Saeed, Faisal; Abdo, Ammar; Salim, Naomie

    2014-01-01

    Molecular similarity is a pervasive concept in drug design. The basic idea underlying molecular similarity is the similar property principle, which states that structurally similar molecules will exhibit similar physicochemical and biological properties. In this paper, a new graph-based molecular descriptor (GBMD) is introduced. The GBMD is a new method of obtaining a rough description of 2D molecular structure in textual form based on the canonical representations of the molecule outline shape and it allows rigorous structure specification using small and natural grammars. Simulated virtual screening experiments with the MDDR database show clearly the superiority of the graph-based descriptor compared to many standard descriptors (ALOGP, MACCS, EPFP4, CDKFP, PCFP, and SMILE) using the Tanimoto coefficient (TAN) and the basic local alignment search tool (BLAST) when searches were carried.

  7. Molecular tectonics: 3-D organisation of decanuclear silver nanoclusters.

    PubMed

    Kozlova, Marina N; Ferlay, Sylvie; Kyritsakas, Nathalie; Hosseini, Mir Wais; Solovieva, Svetlana E; Antipin, Igor S; Konovalov, Alexander I

    2009-05-14

    The combination of silver nitrate with a thiacalix[4]arene derivative bearing at the lower rim four benzonitrile groups leads in the crystalline phase to the formation of a 3-D coordination network in which the organic tectons are connected by decanuclear silver nanoclusters.

  8. Multi-Server Approach for High-Throughput Molecular Descriptors Calculation based on Multi-Linear Algebraic Maps.

    PubMed

    García-Jacas, César R; Aguilera-Mendoza, Longendri; González-Pérez, Reisel; Marrero-Ponce, Yovani; Acevedo-Martínez, Liesner; Barigye, Stephen J; Avdeenko, Tatiana

    2015-01-01

    The present report introduces a novel module of the QuBiLS-MIDAS software for the distributed computation of the 3D Multi-Linear algebraic molecular indices. The main motivation for developing this module is to deal with the computational complexity experienced during the calculation of the descriptors over large datasets. To accomplish this task, a multi-server computing platform named T-arenal was developed, which is suited for institutions with many workstations interconnected through a local network and without resources particularly destined for computation tasks. This new system was deployed in 337 workstations and it was perfectly integrated with the QuBiLS-MIDAS software. To illustrate the usability of the T-arenal platform, performance tests over a dataset comprised of 15 000 compounds are carried out, yielding a 52 and 60 fold reduction in the sequential processing time for the 2-Linear and 3-Linear indices, respectively. Therefore, it can be stated that the T-arenal based distribution of computation tasks constitutes a suitable strategy for performing high-throughput calculations of 3D Multi-Linear descriptors over thousands of chemical structures for posterior QSAR and/or ADME-Tox studies.

  9. Comparison of combinatorial clustering methods on pharmacological data sets represented by machine learning-selected real molecular descriptors.

    PubMed

    Rivera-Borroto, Oscar Miguel; Marrero-Ponce, Yovani; García-de la Vega, José Manuel; Grau-Ábalo, Ricardo del Corazón

    2011-12-27

    Cluster algorithms play an important role in diversity related tasks of modern chemoinformatics, with the widest applications being in pharmaceutical industry drug discovery programs. The performance of these grouping strategies depends on various factors such as molecular representation, mathematical method, algorithmical technique, and statistical distribution of data. For this reason, introduction and comparison of new methods are necessary in order to find the model that best fits the problem at hand. Earlier comparative studies report on Ward's algorithm using fingerprints for molecular description as generally superior in this field. However, problems still remain, i.e., other types of numerical descriptions have been little exploited, current descriptors selection strategy is trial and error-driven, and no previous comparative studies considering a broader domain of the combinatorial methods in grouping chemoinformatic data sets have been conducted. In this work, a comparison between combinatorial methods is performed,with five of them being novel in cheminformatics. The experiments are carried out using eight data sets that are well established and validated in the medical chemistry literature. Each drug data set was represented by real molecular descriptors selected by machine learning techniques, which are consistent with the neighborhood principle. Statistical analysis of the results demonstrates that pharmacological activities of the eight data sets can be modeled with a few of families with 2D and 3D molecular descriptors, avoiding classification problems associated with the presence of nonrelevant features. Three out of five of the proposed cluster algorithms show superior performance over most classical algorithms and are similar (or slightly superior in the most optimistic sense) to Ward's algorithm. The usefulness of these algorithms is also assessed in a comparative experiment to potent QSAR and machine learning classifiers, where they perform

  10. Quantum vs. topological descriptors in the development of molecular models of groundwater pollution by pesticides.

    PubMed

    Worrall, Fred; Thomsen, Marianne

    2004-01-01

    Using monitoring observations from two, independent studies of US groundwater comprising a total of 61 pesticide compounds, this study has shown that those compounds found in groundwater can be distinguished from those that cannot be found in groundwater on the basis of semi-empirical, quantum chemical and empirical molecular descriptors. For the semi-empirical descriptors, logistic regression models have been developed and validated against the dataset based on the semi-empirical and quantum chemical descriptors. Logistic regression models, based on the Debye dipole moment (mu), the hydration energy (DeltaHhyd), and van der Waals volume (VvdW), resulted in a maximal explained variation in the data of 74%. When topological indices were also included the explained variance in data increased to 91%, with 86% of the variation being explained by the rule that a compound will be found in groundwater if: 0.28mu < 6chip(v) where 6chip(v) is the sixth-order molecular path connectivity and mu is the dipole moment of the compound. The significance of the dipole moment and hydration energy (or van der Waals volume) indicates that it is water solubility that controls mobility, with the inclusion of topological descriptors representing structural factors limiting the solubility. The dependence of leaching potential on the descriptors that control solubility indicates that predictions of environmental fate based on this approach may represent a strong alternative to the use of adsorption and degradation parameters.

  11. CBS-QB3 calculation of quantum chemical molecular descriptors of isomeric thiadiazoles.

    PubMed

    Glossman-Mitnik, Daniel

    2006-12-01

    The results of the calculation of several molecular descriptors of isomeric thiadiazoles through the CBS-QB3 model chemistry are presented in this work. The results could be useful in quantitative structure-activity relationship (QSAR) or quantitative structure-property relationship (QSPR) studies of derivatives of the nitrogen-containing analogs of thiophene.

  12. Relationship between molecular descriptors and the enthalpies of sublimation of natural amino acids

    NASA Astrophysics Data System (ADS)

    Badelin, V. G.; Tyunina, V. V.; Girichev, G. V.; Tyunina, E. Yu.

    2016-07-01

    A multiparameter correlation between the enthalpies of sublimation and molecular descriptors of natural amino acids is proposed, based on generalized experimental and literature data on the heat effects of sublimation. The contributions from Van der Waals interactions, hydrogen bond formation, and electrostatic effects into enthalpy of sublimation has been evaluated using regression coefficients.

  13. Prediction of retention in hydrophilic interaction liquid chromatography using solute molecular descriptors based on chemical structures.

    PubMed

    Taraji, Maryam; Haddad, Paul R; Amos, Ruth I J; Talebi, Mohammad; Szucs, Roman; Dolan, John W; Pohl, Christopher A

    2017-02-24

    Quantitative structure-retention relationship (QSRR) models are developed to predict the retention times of analytes on five hydrophilic interaction liquid chromatography (HILIC) stationary phases (bare silica, amine, amide, diol and zwitterionic), with a view to selecting the most suitable stationary phase(s) for the separation of these analytes. The study was conducted using six β-adrenergic agonists as target analytes. Molecular descriptors were calculated based only on chemical structures optimized using density functional theory. A genetic algorithm (GA) was then used to select the most relevant molecular descriptors and these were used to build a retention model for each stationary phase using partial least squares (PLS) regression. This model was then used to predict the retention of the test set of target analytes. This process created an optimized descriptor set which enhanced the reliability of the developed QSRR models. Finally, the QSRR models developed in the work were utilized to provide some insight into the separation mechanisms operating in the HILIC mode. Three performance criteria - mean absolute error (MAE), root mean square error of prediction scaled to retention time (RMSEP), and the number of selected descriptors, were used to evaluate the developed models when applied to an external test set of six β-adrenergic agonists and showed highly predictive abilities. MAE values ranged from 13 to 25s on four of the stationary phases, with a somewhat higher error (50s) being observed for the zwitterionic phase. RMSEP values of 4.88-11.12% were recorded. Validation was performed through Y-randomization and chemical domain applicability, from which it was evident that the developed optimized GA-PLS models were robust. The high levels of accuracy, reliability and applicability of the models were to a large extent due to the optimization of the GA descriptor set and the presence of relevant structural and geometric molecular descriptors, together with

  14. Categorical prototyping: incorporating molecular mechanisms into 3D printing

    NASA Astrophysics Data System (ADS)

    Brommer, Dieter B.; Giesa, Tristan; Spivak, David I.; Buehler, Markus J.

    2016-01-01

    We apply the mathematical framework of category theory to articulate the precise relation between the structure and mechanics of a nanoscale system in a macroscopic domain. We maintain the chosen molecular mechanical properties from the nanoscale to the continuum scale. Therein we demonstrate a procedure to ‘protoype a model’, as category theory enables us to maintain certain information across disparate fields of study, distinct scales, or physical realizations. This process fits naturally with prototyping, as a prototype is not a complete product but rather a reduction to test a subset of properties. To illustrate this point, we use large-scale multi-material printing to examine the scaling of the elastic modulus of 2D carbon allotropes at the macroscale and validate our printed model using experimental testing. The resulting hand-held materials can be examined more readily, and yield insights beyond those available in the original digital representations. We demonstrate this concept by twisting the material, a test beyond the scope of the original model. The method developed can be extended to other methods of additive manufacturing.

  15. Categorical prototyping: incorporating molecular mechanisms into 3D printing.

    PubMed

    Brommer, Dieter B; Giesa, Tristan; Spivak, David I; Buehler, Markus J

    2016-01-15

    We apply the mathematical framework of category theory to articulate the precise relation between the structure and mechanics of a nanoscale system in a macroscopic domain. We maintain the chosen molecular mechanical properties from the nanoscale to the continuum scale. Therein we demonstrate a procedure to 'protoype a model', as category theory enables us to maintain certain information across disparate fields of study, distinct scales, or physical realizations. This process fits naturally with prototyping, as a prototype is not a complete product but rather a reduction to test a subset of properties. To illustrate this point, we use large-scale multi-material printing to examine the scaling of the elastic modulus of 2D carbon allotropes at the macroscale and validate our printed model using experimental testing. The resulting hand-held materials can be examined more readily, and yield insights beyond those available in the original digital representations. We demonstrate this concept by twisting the material, a test beyond the scope of the original model. The method developed can be extended to other methods of additive manufacturing.

  16. Local indices for similarity analysis (LISA)-a 3D-QSAR formalism based on local molecular similarity.

    PubMed

    Verma, Jitender; Malde, Alpeshkumar; Khedkar, Santosh; Iyer, Radhakrishnan; Coutinho, Evans

    2009-12-01

    A simple quantitative structure activity relationship (QSAR) approach termed local indices for similarity analysis (LISA) has been developed. In this technique, the global molecular similarity is broken up as local similarity at each grid point surrounding the molecules and is used as a QSAR descriptor. In this way, a view of the molecular sites permitting favorable and rational changes to enhance activity is obtained. The local similarity index, calculated on the basis of Petke's formula, segregates the regions into "equivalent", "favored similar", and "disfavored similar" (alternatively "favored dissimilar") potentials with respect to a reference molecule in the data set. The method has been tested on three large and diverse data sets-thrombin, glycogen phosphorylase b, and thermolysin inhibitors. The QSAR models derived using genetic algorithm incorporated partial least square analysis statistics are found to be comparable to the ones obtained by the standard three-dimensional (3D)-QSAR methods, such as comparative molecular field analysis and comparative molecular similarity indices analysis. The graphical interpretation of the LISA models is straightforward, and the outcome of the models corroborates well with literature data. The LISA models give insight into the binding mechanisms of the ligand with the enzyme and allow fine-tuning of the molecules at the local level to improve their activity.

  17. ProteinVista: a fast molecular visualization system using Microsoft Direct3D.

    PubMed

    Park, Chan-Yong; Park, Sung-Hee; Park, Soo-Jun; Park, Sun-Hee; Hwang, Chi-Jung

    2008-09-01

    Many tools have been developed to visualize protein and molecular structures. Most high quality protein visualization tools use the OpenGL graphics library as a 3D graphics system. Currently, the performance of recent 3D graphics hardware has rapidly improved. Recent high-performance 3D graphics hardware support Microsoft Direct3D graphics library more than OpenGL and have become very popular in personal computers (PCs). In this paper, a molecular visualization system termed ProteinVista is proposed. ProteinVista is well-designed visualization system using the Microsoft Direct3D graphics library. It provides various visualization styles such as the wireframe, stick, ball and stick, space fill, ribbon, and surface model styles, in addition to display options for 3D visualization. As ProteinVista is optimized for recent 3D graphics hardware platforms and because it uses a geometry instancing technique, its rendering speed is 2.7 times faster compared to other visualization tools.

  18. Correlating 3D morphology with molecular pathology: fibrotic remodelling in human lung biopsies.

    PubMed

    Kellner, Manuela; Wehling, Judith; Warnecke, Gregor; Heidrich, Marko; Izykowski, Nicole; Vogel-Claussen, Jens; Lorbeer, Raoul-Amadeus; Antonopoulos, Georgios; Janciauskiene, Sabina; Grothausmann, Roman; Knudsen, Lars; Ripken, Tammo; Meyer, Heiko; Kreipe, Hans; Ochs, Matthias; Jonigk, Danny; Kühnel, Mark Philipp

    2015-12-01

    Assessing alterations of the parenchymal architecture is essential in understanding fibrosing interstitial lung diseases. Here, we present a novel method to visualise fibrotic remodelling in human lungs and correlate morphological three-dimensional (3D) data with gene and protein expression in the very same sample. The key to our approach is a novel embedding resin that clears samples to full optical transparency and simultaneously allows 3D laser tomography and preparation of sections for histology, immunohistochemistry and RNA isolation. Correlating 3D laser tomography with molecular diagnostic techniques enables new insights into lung diseases. This approach has great potential to become an essential tool in pulmonary research.

  19. On an aspect of calculated molecular descriptors in QSAR studies of quinolone antibacterials.

    PubMed

    Ghosh, Payel; Thanadath, Megha; Bagchi, Manish C

    2006-08-01

    The re-emergence of tuberculosis infections, which are resistant to conventional drug therapy, has steadily risen in the last decade and as a result of that, fluoroquinolone drugs are being used as the second line of action. But there is hardly any study to examine specific structure activity relationships of quinolone antibacterials against mycobacteria. In this paper, an attempt has been made to establish a quantitative structure activity relationship modeling for a series of quinolone compounds against Mycobacterium fortuitum and Mycobacterium smegmatis. Due to lack of sufficient physicochemical data for the anti-mycobacterial compounds, it becomes very difficult to develop predictive methods based on experimental data. The present paper is an effort for the development of QSARs from the standpoint of physicochemical, constitutional, geometrical, electrostatic and topological indices. Molecular descriptors have been calculated solely from the chemical structure of N-1, C-7 and 8 substituted quinolone compounds and ridge regression models have been developed which can explain a better structure-activity relationship. Consideration of an intermolecular similarity analysis approach that led to a successful computer program development in PERL language has been used for comparing the influence of various molecular descriptors in different data subsets. The comparison of relative effectiveness of the calculated descriptors in our ridge regression model gives rise to some interesting results.

  20. Aquifer vulnerability to pesticide pollution - Combining soil, land-use and aquifer properties with molecular descriptors

    USGS Publications Warehouse

    Worrall, F.; Kolpin, D.W.

    2004-01-01

    This study uses an extensive survey of herbicides in groundwater across the midwest United States to predict occurrences of a range of compounds across the region from a combination of their molecular properties and the properties of the catchment of a borehole. The study covers 100 boreholes and eight pesticides. For each of the boreholes its catchment the soil, land-use and aquifer properties were characterized. Discriminating boreholes where pollution occurred from those where no pollution occurred gave a model that was 74% correct with organic carbon content, percentage sand content and depth to the water table being significant properties of the borehole catchment. Molecular topological descriptors as well as Koc, solubility and half-life were used to characterize each compound included in the study. Inclusion of molecular properties makes it possible to discriminate between occurrence and non-occurrence of each compound in each well. The best-fit model combines: organic carbon content, percentage sand content and depth to the water table with molecular descriptors representing molecular size, molecular branching and functional group composition of the herbicides.

  1. DYNAMIC 3D QSAR TECHNIQUES: APPLICATIONS IN TOXICOLOGY

    EPA Science Inventory

    Two dynamic techniques recently developed to account for conformational flexibility of chemicals in 3D QSARs are presented. In addition to the impact of conformational flexibility of chemicals in 3D QSAR models, the applicability of various molecular descriptors is discussed. The...

  2. Dissecting molecular descriptors into atomic contributions in density functional reactivity theory.

    PubMed

    Rong, Chunying; Lu, Tian; Liu, Shubin

    2014-01-14

    Density functional reactivity theory (DFRT) employs the electron density of a molecule and its related quantities such as gradient and Laplacian to describe its structure and reactivity properties. Proper descriptions at both molecular (global) and atomic (local) levels are equally important and illuminating. In this work, we make use of Bader's zero-flux partition scheme and consider atomic contributions for a few global reactivity descriptors in DFRT, including the density-based quantification of steric effect and related indices. Earlier, we proved that these quantities are intrinsically correlated for atomic and molecular systems [S. B. Liu, J. Chem. Phys. 126, 191107 (2007); ibid. 126, 244103 (2007)]. In this work, a new basin-based integration algorithm has been implemented, whose reliability and effectiveness have been extensively examined. We also investigated a list of simple hydrocarbon systems and different scenarios of bonding processes, including stretching, bending, and rotating. Interesting changing patterns for the atomic and molecular values of these quantities have been revealed for different systems. This work not only confirms the strong correlation between these global reactivity descriptors for molecular systems, as theoretically proven earlier by us, it also provides new and unexpected changing patterns for their atomic values, which can be employed to understand the origin and nature of chemical phenomena.

  3. Alkynes as a versatile platform for construction of chemical molecular complexity and realization of molecular 3D printing

    NASA Astrophysics Data System (ADS)

    Galkin, K. I.; Ananikov, V. P.

    2016-03-01

    The current level of scientific and technological development requires the formation of general tools and techniques. One of the most versatile technologies is 3D printing, which allows fast and efficient creation of materials and biological objects of desired shape and composition. Today, methods have been developed for 3D printing of macro- and nano-sized objects and for production of films and deposited materials with molecular precision but the most promising technology is printing at the molecular level (molecular 3D printing) for the purpose of direct construction of molecular complexity. This process is currently at the initial stage concerning selection of simple molecules to be used as building blocks possessing flexibility, availability and ease of modification. In this review, we examine the possible versatile synthons suitable for preparation of the main types of organic compounds using molecular 3D printing. The surveyed data strongly indicate that alkyne molecules may be used as a building material in a molecular 3D printer working on hydrocarbons. The bibliography includes 428 references.

  4. Mapping molecular orientational distributions for biological sample in 3D (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    HE, Wei; Ferrand, Patrick; Richter, Benjamin; Bastmeyer, Martin; Brasselet, Sophie

    2016-04-01

    Measuring molecular orientation properties is very appealing for scientists in molecular and cell biology, as well as biomedical research. Orientational organization at the molecular scale is indeed an important brick to cells and tissues morphology, mechanics, functions and pathologies. Recent work has shown that polarized fluorescence imaging, based on excitation polarization tuning in the sample plane, is able to probe molecular orientational order in biological samples; however this applies only to information in 2D, projected in the sample plane. To surpass this limitation, we extended this approach to excitation polarization tuning in 3D. The principle is based on the decomposition of any arbitrary 3D linear excitation in a polarization along the longitudinal z-axis, and a polarization in the transverse xy-sample plane. We designed an interferometer with one arm generating radial polarization light (thus producing longitudinal polarization under high numerical aperture focusing), the other arm controlling a linear polarization in the transverse plane. The amplitude ratio between the two arms can vary so as to get any linear polarized excitation in 3D at the focus of a high NA objective. This technique has been characterized by polarimetry imaging at the back focal plane of the focusing objective, and modeled theoretically. 3D polarized fluorescence microscopy is demonstrated on actin stress fibers in non-flat cells suspended on synthetic polymer structures forming supporting pillars, for which heterogeneous actin orientational order could be identified. This technique shows a great potential in structural investigations in 3D biological systems, such as cell spheroids and tissues.

  5. Building Proteins in a Day: Efficient 3D Molecular Structure Estimation with Electron Cryomicroscopy.

    PubMed

    Punjani, Ali; Brubaker, Marcus A; Fleet, David J

    2017-04-01

    Discovering the 3D atomic-resolution structure of molecules such as proteins and viruses is one of the foremost research problems in biology and medicine. Electron Cryomicroscopy (cryo-EM) is a promising vision-based technique for structure estimation which attempts to reconstruct 3D atomic structures from a large set of 2D transmission electron microscope images. This paper presents a new Bayesian framework for cryo-EM structure estimation that builds on modern stochastic optimization techniques to allow one to scale to very large datasets. We also introduce a novel Monte-Carlo technique that reduces the cost of evaluating the objective function during optimization by over five orders of magnitude. The net result is an approach capable of estimating 3D molecular structure from large-scale datasets in about a day on a single CPU workstation.

  6. Quantitative structure-activity relationship of organophosphate compounds based on molecular interaction fields descriptors.

    PubMed

    Zhao, Jinsong; Yu, Shuxia

    2013-03-01

    By using multi-block partial least-squares (MBPLS) method, quantitative structure-activity relationship (QSAR) between 35 organophosphate compounds (OP) and their 24h acute toxicities towards the housefly (Musca nebulo L.) was built on the molecular interaction fields (MIF) descriptors, which were obtained with O, N and DRY as probes, and then normalised with block unscaled weights (BUW) technique. The best QSAR model had 8 principal components, with the coefficient of determination R(2)=0.995 and that of leave-one-out cross-validation Q(2)=0.865, and the corresponding standard deviation of error 0.076 and 0.361, respectively. Block importance in the prediction (BIP) for O, N and DRY probe were 1.030, 0.962 and 1.007, respectively. Contour map of variable coefficients showed that hydrogen bonding between the O atom in PO and the NH groups in acetylcholinesterase (AChE) played an important role in the interaction between OP and AChE. Meanwhile, the hydrophobicity of OP also had significant contribution. QSAR based on the MIF descriptors could be a potential means to interpret the mechanisms of ligand-receptor interaction when the receptor was well known.

  7. Reactivity Descriptors for the Activity of Molecular MN4 Catalysts for the Oxygen Reduction Reaction.

    PubMed

    Zagal, José H; Koper, Marc T M

    2016-11-14

    Similarities are established between well-known reactivity descriptors of metal electrodes for their activity in the oxygen reduction reaction (ORR) and the reactivity of molecular catalysts, in particular macrocyclic MN4 metal complexes confined to electrode surfaces. We show that there is a correlation between the M(III) /M(II) redox potential of MN4 chelates and the M-O2 binding energies. Specifically, the binding energy of O2 (and other O species) follows the M(III) -OH/M(II) redox transition for MnN4 and FeN4 chelates. The ORR volcano plot for MN4 catalysts is similar to that for metal catalysts: catalysts on the weak binding side (mostly CoN4 chelates) yield mainly H2 O2 as the product, with an ORR onset potential independent of the pH value on the NHE scale (and therefore pH-dependent on the RHE scale); catalysts on the stronger binding side yield H2 O as the product with the expected pH-dependence on the NHE scale. The suggested descriptors also apply to heat-treated pyrolyzed MN4 catalysts.

  8. Chemical and Molecular Descriptors for the Reactivity of Amines with CO{sub 2}

    SciTech Connect

    Lee, Anita S.; Kitchin, John R.

    2012-10-24

    Amine-based solvents are likely to play an important role in CO{sub 2} capture applications in the future, and the identification of amines with superior performance will facilitate their use in CO{sub 2} capture. While some improvements in performance will be achieved through process modifications, modifying the CO{sub 2} capture performance of an amine also implies in part an ability to modify the reactions between the amine and CO{sub 2} through development of new functionalized amines. We present a computational study of trends in the reactions between CO{sub 2} and functionalized amines with a focus on identifying molecular descriptors that determine trends in reactivity. We examine the formation of bicarbonate and carbamate species on three classes of functionalized amines: alkylamines, alkanolamines, and fluorinated alkylamines including primary, secondary and tertiary amines in each class. These functional groups span electron-withdrawing to donating behavior, hydrogen-bonding, extent of functionalization, and proximity effects of the functional groups. Electron withdrawing groups tend to destabilize CO{sub 2} reaction products, whereas electron-donating groups tend to stabilize CO{sub 2} reaction products. Hydrogen bonding stabilizes CO{sub 2} reaction products. Electronic structure descriptors based on electronegativity were found to describe trends in the bicarbonate formation energy. A chemical correlation was observed between the carbamate formation energy and the carbamic acid formation energy. The local softness on the reacting N in the amine was found to partially explain trends carbamic acid formation energy.

  9. Molecular interaction study of flavonoid derivative 3d with human serum albumin using multispectroscopic and molecular modeling approach.

    PubMed

    Wei, Juntong; Jin, Feng; Wu, Qin; Jiang, Yuyang; Gao, Dan; Liu, Hongxia

    2014-08-01

    Human serum albumin (HSA) has been developed as a model protein to study drug-protein interaction. In the present work, the interaction between our synthesized flavonoid derivative 3d (possessing potent antitumor activity against HepG2 cells) and HSA was investigated using fluorescence spectroscopy, circular dichroism spectroscopy, UV-vis spectroscopy and molecular modeling approach. Fluorescence spectroscopy showed that the fluorescence of HSA can be quenched remarkably by 3d under physiological condition with a slight shift of maximum fluorescence emission bands from 360nm to 363nm. Calculated results from Stern-Volmer equation and modified Stern-Volmer equation indicated that the fluorescence was quenched by static quenching processing with association constant 5.26±0.04×10(4)L mol(-1) at 298K. After comprehensive consideration of the free energy change ΔG, enthalpy change ΔH and entropy change ΔS, electrostatic interactions were confirmed as the main factor that participate in stabilizing the 3d-HSA complex. Both dichroism spectroscopy and UV-vis spectroscopy indicated conformational change of HSA after binding to 3d. Moreover, the structure of HSA was loosened and the percentage of α-helix decreased with increasing concentration of 3d. Molecular modeling results demonstrated that 3d could bind to HSA well into subdomain IIA, which is related to its capability of deposition and delivery. Three cation-π interactions and three hydrogen bonds occurred between 3d and amino acid residuals ARG218, ARG222 and LYS199. In conclusion, flavonoid derivative 3d can bind to HSA with noncovalent bond in a relatively stable way, so it can be delivered by HSA in a circulatory system.

  10. Quantitative structure-activity relationship modeling of polycyclic aromatic hydrocarbon mutagenicity by classification methods based on holistic theoretical molecular descriptors.

    PubMed

    Gramatica, Paola; Papa, Ester; Marrocchi, Assunta; Minuti, Lucio; Taticchi, Aldo

    2007-03-01

    Various polycyclic aromatic hydrocarbons (PAHs), ubiquitous environmental pollutants, are recognized mutagens and carcinogens. A homogeneous set of mutagenicity data (TA98 and TA100,+S9) for 32 benzocyclopentaphenanthrenes/chrysenes was modeled by the quantitative structure-activity relationship classification methods k-nearest neighbor and classification and regression tree, using theoretical holistic molecular descriptors. Genetic algorithm provided the selection of the best subset of variables for modeling mutagenicity. The models were validated by leave-one-out and leave-50%-out approaches and have good performance, with sensitivity and specificity ranges of 90-100%. Mutagenicity assessment for these PAHs requires only a few theoretical descriptors of their molecular structure.

  11. Reticular synthesis of porous molecular 1D nanotubes and 3D networks

    NASA Astrophysics Data System (ADS)

    Slater, A. G.; Little, M. A.; Pulido, A.; Chong, S. Y.; Holden, D.; Chen, L.; Morgan, C.; Wu, X.; Cheng, G.; Clowes, R.; Briggs, M. E.; Hasell, T.; Jelfs, K. E.; Day, G. M.; Cooper, A. I.

    2017-01-01

    Synthetic control over pore size and pore connectivity is the crowning achievement for porous metal-organic frameworks (MOFs). The same level of control has not been achieved for molecular crystals, which are not defined by strong, directional intermolecular coordination bonds. Hence, molecular crystallization is inherently less controllable than framework crystallization, and there are fewer examples of 'reticular synthesis', in which multiple building blocks can be assembled according to a common assembly motif. Here we apply a chiral recognition strategy to a new family of tubular covalent cages to create both 1D porous nanotubes and 3D diamondoid pillared porous networks. The diamondoid networks are analogous to MOFs prepared from tetrahedral metal nodes and linear ditopic organic linkers. The crystal structures can be rationalized by computational lattice-energy searches, which provide an in silico screening method to evaluate candidate molecular building blocks. These results are a blueprint for applying the 'node and strut' principles of reticular synthesis to molecular crystals.

  12. EVA: A new theoretically based molecular descriptor for use in QSAR/QSPR analysis

    NASA Astrophysics Data System (ADS)

    Ferguson, A. M.; Heritage, T.; Jonathon, P.; Pack, S. E.; Phillips, L.; Rogan, J.; Snaith, P. J.

    1997-03-01

    A new descriptor of molecular structure, EVA, for use in the derivation of robustly predictive QSAR relationships is described. It is based on theoretically derived normal coordinate frequencies, and has been used extensively and successfully in proprietary chemical discovery programmes within Shell Research. As a result of informal dissemination of the methodology, it is now being used successfully in related areas such as pharmaceutical drug discovery. Much of the experimental data used in development remain proprietary, and are not available for publication. This paper describes the method and illustrates its application to the calculation of nonproprietary data, log Pow, in both explanatory and predictive modes. It will be followed by other publications illustrating its application to a range of data derived from biological systems.

  13. Prioritization of in silico models and molecular descriptors for the assessment of ready biodegradability.

    PubMed

    Fernández, Alberto; Rallo, Robert; Giralt, Francesc

    2015-10-01

    Ready biodegradability is a key property for evaluating the long-term effects of chemicals on the environment and human health. As such, it is used as a screening test for the assessment of persistent, bioaccumulative and toxic substances. Regulators encourage the use of non-testing methods, such as in silico models, to save money and time. A dataset of 757 chemicals was collected to assess the performance of four freely available in silico models that predict ready biodegradability. They were applied to develop a new consensus method that prioritizes the use of each individual model according to its performance on chemical subsets driven by the presence or absence of different molecular descriptors. This consensus method was capable of almost eliminating unpredictable chemicals, while the performance of combined models was substantially improved with respect to that of the individual models.

  14. Parallel implementation of 3D FFT with volumetric decomposition schemes for efficient molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Jung, Jaewoon; Kobayashi, Chigusa; Imamura, Toshiyuki; Sugita, Yuji

    2016-03-01

    Three-dimensional Fast Fourier Transform (3D FFT) plays an important role in a wide variety of computer simulations and data analyses, including molecular dynamics (MD) simulations. In this study, we develop hybrid (MPI+OpenMP) parallelization schemes of 3D FFT based on two new volumetric decompositions, mainly for the particle mesh Ewald (PME) calculation in MD simulations. In one scheme, (1d_Alltoall), five all-to-all communications in one dimension are carried out, and in the other, (2d_Alltoall), one two-dimensional all-to-all communication is combined with two all-to-all communications in one dimension. 2d_Alltoall is similar to the conventional volumetric decomposition scheme. We performed benchmark tests of 3D FFT for the systems with different grid sizes using a large number of processors on the K computer in RIKEN AICS. The two schemes show comparable performances, and are better than existing 3D FFTs. The performances of 1d_Alltoall and 2d_Alltoall depend on the supercomputer network system and number of processors in each dimension. There is enough leeway for users to optimize performance for their conditions. In the PME method, short-range real-space interactions as well as long-range reciprocal-space interactions are calculated. Our volumetric decomposition schemes are particularly useful when used in conjunction with the recently developed midpoint cell method for short-range interactions, due to the same decompositions of real and reciprocal spaces. The 1d_Alltoall scheme of 3D FFT takes 4.7 ms to simulate one MD cycle for a virus system containing more than 1 million atoms using 32,768 cores on the K computer.

  15. Mass Spectrometry Based Molecular 3D-Cartography of Plant Metabolites

    PubMed Central

    Floros, Dimitrios J.; Petras, Daniel; Kapono, Clifford A.; Melnik, Alexey V.; Ling, Tie-Jun; Knight, Rob; Dorrestein, Pieter C.

    2017-01-01

    Plants play an essential part in global carbon fixing through photosynthesis and are the primary food and energy source for humans. Understanding them thoroughly is therefore of highest interest for humanity. Advances in DNA and RNA sequencing and in protein and metabolite analysis allow the systematic description of plant composition at the molecular level. With imaging mass spectrometry, we can now add a spatial level, typically in the micrometer-to-centimeter range, to their compositions, essential for a detailed molecular understanding. Here we present an LC-MS based approach for 3D plant imaging, which is scalable and allows the analysis of entire plants. We applied this approach in a case study to pepper and tomato plants. Together with MS/MS spectra library matching and spectral networking, this non-targeted workflow provides the highest sensitivity and selectivity for the molecular annotations and imaging of plants, laying the foundation for studies of plant metabolism and plant-environment interactions.

  16. Quantitative 3D molecular cutaneous absorption in human skin using label free nonlinear microscopy.

    PubMed

    Chen, Xueqin; Grégoire, Sébastien; Formanek, Florian; Galey, Jean-Baptiste; Rigneault, Hervé

    2015-02-28

    Understanding the penetration mechanisms of drugs into human skin is a key issue in pharmaceutical and cosmetics research. To date, the techniques available for percutaneous penetration of compounds fail to provide a quantitative 3D map of molecular concentration distribution in complex tissues as the detected microscopy images are an intricate combination of concentration distribution and laser beam attenuation upon deep penetration. Here we introduce and validate a novel framework for imaging and reconstructing molecular concentration within the depth of artificial and human skin samples. Our approach combines the use of deuterated molecular compounds together with coherent anti-Stokes Raman scattering spectroscopy and microscopy that permits targeted molecules to be unambiguously discriminated within skin layers. We demonstrate both intercellular and transcellular pathways for different active compounds, together with in-depth concentration profiles reflecting the detailed skin barrier architecture. This method provides an enabling platform for establishing functional activity of topically applied products.

  17. Foldectures: 3D Molecular Architectures from Self-Assembly of Peptide Foldamers.

    PubMed

    Yoo, Sung Hyun; Lee, Hee-Seung

    2017-02-13

    The wide range of fascinating supramolecular architectures found in nature, from DNA double helices to giant protein shells, inspires researchers to mimic the diverse shapes and functions of natural systems. Thus, a variety of artificial molecular platforms have been developed by assembling DNA-, peptide-, and protein-based building blocks for medicinal and biological applications. There has also been a significant interest in the research of non-natural oligomers (i.e., foldamers) that fold into well-defined secondary structures analogous to those found in proteins, because the assemblies of foldamers are expected not only to form biomimetic supramolecular architectures that resemble those of nature but also to display unique functions and unprecedented topologies at the same time due to their different folding propensities from those of natural building blocks. Foldamer-based supramolecular architectures have been reported in the form of nanofibers, nanochannels, nanosheets, and finite three-dimensional (3D) shapes. We have developed a new class of crystalline peptidic materials termed "foldectures" (a compound of foldamer and architecture) with unprecedented topological complexity derived from the rapid and nonequilibrium aqueous phase self-assembly of foldamers. In this Account, we discuss the morphological features, molecular packing structures, physical properties, and potential applications of foldectures. Foldectures exhibit well-defined, microscale, homogeneous, and finite structures with unique morphologies such as windmill, tooth, and trigonal bipyramid shapes. The symmetry elements of the morphologies vary with the foldamer building blocks and are retained upon surfactant-assisted shape evolution. Structural characterization by powder X-ray diffraction (PXRD) revealed the molecular packing structures, suggesting how the foldamer building blocks assembled in the 3D structure. The analysis by PXRD showed that intermolecular hydrogen bonding connects

  18. A tetraphenylethylene core-based 3D structure small molecular acceptor enabling efficient non-fullerene organic solar cells.

    PubMed

    Liu, Yuhang; Mu, Cheng; Jiang, Kui; Zhao, Jingbo; Li, Yunke; Zhang, Lu; Li, Zhengke; Lai, Joshua Yuk Lin; Hu, Huawei; Ma, Tingxuan; Hu, Rongrong; Yu, Demei; Huang, Xuhui; Tang, Ben Zhong; Yan, He

    2015-02-01

    A tetraphenylethylene core-based small molecular acceptor with a unique 3D molecular structure is developed. Bulk-heterojunction blend films with a small feature size (≈20 nm) are obtained, which lead to non-fullerene organic solar cells (OSCs) with 5.5% power conversion efficiency. The work provides a new molecular design approach to efficient non-fullerene OSCs based on 3D-structured small-molecule acceptors.

  19. Development of 3D-QSAR Model for Acetylcholinesterase Inhibitors Using a Combination of Fingerprint, Molecular Docking, and Structure-Based Pharmacophore Approaches.

    PubMed

    Lee, Sehan; Barron, Mace G

    2015-11-01

    Acetylcholinesterase (AChE), a serine hydrolase vital for regulating the neurotransmitter acetylcholine in animals, has been used as a target for drugs and pesticides. With the increasing availability of AChE crystal structures, with or without ligands bound, structure-based approaches have been successfully applied to AChE inhibitors (AChEIs). The major limitation of these approaches has been the small applicability domain due to the lack of structural diversity in the training set. In this study, we developed a 3 dimensional quantitative structure-activity relationship (3D-QSAR) for inhibitory activity of 89 reversible and irreversible AChEIs including drugs and insecticides. A 3D-fingerprint descriptor encoding protein-ligand interactions was developed using molecular docking and structure-based pharmacophore to rationalize the structural requirements responsible for the activity of these compounds. The obtained 3D-QSAR model exhibited high correlation value (R(2) = 0.93) and low mean absolute error (MAE = 0.32 log units) for the training set (n = 63). The model was predictive across a range of structures as shown by the leave-one-out cross-validated correlation coefficient (Q(2) = 0.89) and external validation results (n = 26, R(2) = 0.89, and MAE = 0.38 log units). The model revealed that the compounds with high inhibition potency had proper conformation in the active site gorge and interacted with key amino acid residues, in particular Trp84 and Phe330 at the catalytic anionic site, Trp279 at the peripheral anionic site, and Gly118, Gly119, and Ala201 at the oxyanion hole. The resulting universal 3D-QSAR model provides insight into the multiple molecular interactions determining AChEI potency that may guide future chemical design and regulation of toxic AChEIs.

  20. Combined 3D-QSAR modeling and molecular docking study on azacycles CCR5 antagonists

    NASA Astrophysics Data System (ADS)

    Ji, Yongjun; Shu, Mao; Lin, Yong; Wang, Yuanqiang; Wang, Rui; Hu, Yong; Lin, Zhihua

    2013-08-01

    The beta chemokine receptor 5 (CCR5) is an attractive target for pharmaceutical industry in the HIV-1, inflammation and cancer therapeutic areas. In this study, we have developed quantitative structure activity relationship (QSAR) models for a series of 41 azacycles CCR5 antagonists using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and Topomer CoMFA methods. The cross-validated coefficient q2 values of 3D-QASR (CoMFA, CoMSIA, and Topomer CoMFA) methods were 0.630, 0.758, and 0.852, respectively, the non-cross-validated R2 values were 0.979, 0.978, and 0.990, respectively. Docking studies were also employed to determine the most probable binding mode. 3D contour maps and docking results suggested that bulky groups and electron-withdrawing groups on the core part would decrease antiviral activity. Furthermore, docking results indicated that H-bonds and π bonds were favorable for antiviral activities. Finally, a set of novel derivatives with predicted activities were designed.

  1. Theoretical molecular descriptors relevant to the uptake of persistent organic pollutants from soil by zucchini. A QSAR study.

    PubMed

    Bordás, Barna; Bélai, Iván; Koomíves, Tamás

    2011-04-13

    The uptake of persistent organic pollutants (POPs) from soil by plants allows the development of phytoremediation protocols to rehabilitate contaminated areas. The use of diverse theoretical descriptors has been reported in the literature for developing quantitative structure-activity relationship (QSAR) models for predicting the bioconcentration factors (BCFs) of POPs in different plants. In this paper an evaluation is given on the molecular properties of POPs in terms of theoretical molecular descriptors that are relevant to the uptake and accumulation of these persistent pollutants from soil by two zucchini varieties. Statistically significant and predictive linear regression models have been developed for the BCF values of 20 polychlorinated dibenzo-p-dioxins/dibenzofurans and 14 polyhalogenated biphenyls in two zucchini varieties based on retrospective data. The relevant parameters have been selected from a set of 1660 DRAGON, 150 VolSurf, and 11 quantum chemical descriptors. The two most significant regression models, containing VolSurf, DRAGON GETAWAY, and quantum chemical descriptors, displayed the following statistical parameters: (eq 3) n = 27, R(2) = 0.940, q(2) = 0.922, SE = 0.155, F = 392.1; (eq 4) n = 27, R(2) = 0.921, q(2) = 0.898, SE = 0.161, F = 140.4. Predictive capabilities of the equations have been validated by using external validation sets. The QSAR models proposed might contribute to the development of viable soil remediation strategies.

  2. Establishment of an in silico phospholipidosis prediction method using descriptors related to molecular interactions causing phospholipid-compound complex formation.

    PubMed

    Haranosono, Yu; Nemoto, Shingo; Kurata, Masaaki; Sakaki, Hideyuki

    2016-04-01

    Although phospholipidosis (PLD) often affects drug development, there is no convenient in vitro or in vivo test system for PLD detection. In this study, we developed an in silico PLD prediction method based on the PLD-inducing mechanism. We focused on phospholipid (PL)-compound complex formation, which inhibits PL degradation by phospholipase. Thus, we used some molecular interactions, such as electrostatic interactions, hydrophobic interactions, and intermolecular forces, between PL and compounds as descriptors. First, we performed descriptor screening for intermolecular force and then developed a new in silico PLD prediction using descriptors related to molecular interactions. Based on the screening, we identified molecular refraction (MR) as a descriptor of intermolecular force. It is known that ClogP and most-basic pKa can be used for PLD prediction. Thereby, we developed an in silico prediction method using ClogP, most-basic pKa, and MR, which were related to hydrophobic interactions, electrostatic interactions, and intermolecular forces. In addition, a resampling method was used to determine the cut-off values for each descriptor. We obtained good results for 77 compounds as follows: sensitivity = 95.8%, specificity = 75.9%, and concordance = 88.3%. Although there is a concern regarding false-negative compounds for pKa calculations, this predictive ability will be adequate for PLD screening. In conclusion, the mechanism-based in silico PLD prediction method provided good prediction ability, and this method will be useful for evaluating the potential of drugs to cause PLD, particularly in the early stage of drug development, because this method only requires knowledge of the chemical structure.

  3. Molecular Determinants of Juvenile Hormone Action as Revealed by 3D QSAR Analysis in Drosophila

    PubMed Central

    Beňo, Milan; Farkaš, Robert

    2009-01-01

    Background Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH). While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. Methodology/Principal Findings To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen) at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 Å or longer than 13.5 Å, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. Conclusions/Significance The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions. PMID:19547707

  4. Time slicing in 3D momentum imaging of the hydrogen molecular ion photo-fragmentation

    NASA Astrophysics Data System (ADS)

    Kaya, N.; Kaya, G.; Pham, F. V.; Strohaber, J.; Kolomenskii, A. A.; Schuessler, H. A.

    2017-02-01

    Photo-fragmentation of the hydrogen molecular ion was investigated with 800 nm, 50 fs laser pulses by employing a time slicing 3D imaging technique that enables the simultaneous measurement of all three momentum components which are linearly related with the pixel position and slicing time. This is done for each individual product particle arriving at the detector. This mode of detection allows us to directly measure the three-dimensional fragment momentum vector distribution without having to rely on mathematical reconstruction methods, which additionally require the investigated system to be cylindrically symmetric. We experimentally reconstruct the laser-induced photo-fragmentation of the hydrogen molecular ion. In previous experiments, neutral molecules were used as a target, but in this work, performed with molecular ions, the initial vibrational level populations are well-defined after electron bombardment, which facilitates the interpretation. We show that the employed time-slicing technique allows us to register the fragment momentum distribution that reflects the initial molecular states with greater detail, revealing features that were concealed in the full time-integrated distribution on the detector.

  5. Observing molecular dynamics with time-resolved 3D momentum imaging

    NASA Astrophysics Data System (ADS)

    Sturm, F. P.; Wright, T.; Bocharova, I.; Ray, D.; Shivaram, N.; Cryan, J.; Belkacem, A.; Weber, T.; Dörner, R.

    2014-05-01

    Photo-excitation and ionization trigger rich dynamics in molecular systems which play a key role in many important processes in nature such as vision, photosynthesis or photoprotection. Observing those reactions in real-time without significantly disturbing the molecules by a strong electric field has been a great challenge. Recent experiments using Time-of-Flight and Velocity Map Imaging techniques have revealed important information on the dynamics of small molecular systems upon photo-excitation. We have developed an apparatus for time-resolved momentum imaging of electrons and ions in all three spatial dimensions that employs two-color femtosecond laser pulses in the vacuum and extreme ultraviolet (VUV, XUV) for probing molecular dynamics. Our COLTRIMS style reaction microscope can measure electrons and ions in coincidence and reconstruct the momenta of the reaction fragments in 3D. We use a high power 800 nm laser in a loose focusing geometry gas cell to efficinetly drive High Harmonic Generation. The resulting photon flux is sufficient to perform 2-photon pump-probe experiments using VUV and XUV pulses for both pump and probe. With this setup we investigate non-Born-Oppenheimer dynamics in small molecules such as C2H4 and CO2 on a femtosecond time scale. Supported by Chemical Sciences, Geosciences and Biosciences division of BES/DOE.

  6. 3D-QSAR and molecular modeling of HIV-1 integrase inhibitors

    NASA Astrophysics Data System (ADS)

    Makhija, Mahindra T.; Kulkarni, Vithal M.

    2002-03-01

    Three-dimensional quantitative structure-activity relationship (3D QSAR) methods were applied on a series of inhibitors of HIV-1 integrase with respect to their inhibition of 3'-processing and 3'-end joining steps in vitro.The training set consisted of 27 compounds belonging to the class of thiazolothiazepines. The predictive ability of each model was evaluated using test set I consisting of four thiazolothiazepines and test set II comprised of seven compounds belonging to an entirely different structural class of coumarins. Maximum Common Substructure (MCS) based method was used to align the molecules and this was compared with other known methods of alignment. Two methods of 3D QSAR: comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were analyzed in terms of their predictive abilities. CoMSIA produced significantly better results for all correlations. The results indicate a strong correlation between the inhibitory activity of these compounds and the steric and electrostatic fields around them. CoMSIA models with considerable internal as well as external predictive ability were obtained. A poor correlation obtained with hydrophobic field indicates that the binding of thiazolothiazepines to HIV-1 integrase is mainly enthalpic in nature. Further the most active compound of the series was docked into the active site using the crystal structure of integrase. The binding site was formed by the amino acid residues 64-67, 116, 148, 151-152, 155-156, and 159. The comparison of coefficient contour maps with the steric and electrostatic properties of the receptor shows high level of compatibility.

  7. 3D-QSAR and molecular docking studies on HIV protease inhibitors

    NASA Astrophysics Data System (ADS)

    Tong, Jianbo; Wu, Yingji; Bai, Min; Zhan, Pei

    2017-02-01

    In order to well understand the chemical-biological interactions governing their activities toward HIV protease activity, QSAR models of 34 cyclic-urea derivatives with inhibitory HIV were developed. The quantitative structure activity relationship (QSAR) model was built by using comparative molecular similarity indices analysis (CoMSIA) technique. And the best CoMSIA model has rcv2, rncv2 values of 0.586 and 0.931 for cross-validated and non-cross-validated. The predictive ability of CoMSIA model was further validated by a test set of 7 compounds, giving rpred2 value of 0.973. Docking studies were used to find the actual conformations of chemicals in active site of HIV protease, as well as the binding mode pattern to the binding site in protease enzyme. The information provided by 3D-QSAR model and molecular docking may lead to a better understanding of the structural requirements of 34 cyclic-urea derivatives and help to design potential anti-HIV protease molecules.

  8. The 3D-QSAR study of 110 diverse, dual binding, acetylcholinesterase inhibitors based on alignment independent descriptors (GRIND-2). The effects of conformation on predictive power and interpretability of the models.

    PubMed

    Vitorović-Todorović, Maja D; Cvijetić, Ilija N; Juranić, Ivan O; Drakulić, Branko J

    2012-09-01

    The 3D-QSAR analysis based on alignment independent descriptors (GRIND-2) was performed on the set of 110 structurally diverse, dual binding AChE reversible inhibitors. Three separate models were built, based on different conformations, generated following next criteria: (i) minimum energy conformations, (ii) conformation most similar to the co-crystalized ligand conformation, and (iii) docked conformation. We found that regardless on conformation used, all the three models had good statistic and predictivity. The models revealed the importance of protonated pyridine nitrogen of tacrine moiety for anti AChE activity, and recognized HBA and HBD interactions as highly important for the potency. This was revealed by the variables associated with protonated pyridinium nitrogen, and the two amino groups of the linker. MIFs calculated with the N1 (pyridinium nitrogen) and the DRY GRID probes in the AChE active site enabled us to establish the relationship between amino acid residues within AChE active site and the variables having high impact on models. External predictive power of the models was tested on the set of 40 AChE reversible inhibitors, most of them structurally different from the training set. Some of those compounds were tested on the different enzyme source. We found that external predictivity was highly sensitive on conformations used. Model based on docked conformations had superior predictive ability, emphasizing the need for the employment of conformations built by taking into account geometrical restrictions of AChE active site gorge.

  9. Optically directed molecular transport and 3D isoelectric positioning of amphoteric biomolecules

    PubMed Central

    Hafeman, Dean G.; Harkins, James B.; Witkowski, Charles E.; Lewis, Nathan S.; Warmack, Robert J.; Brown, Gilbert M.; Thundat, Thomas

    2006-01-01

    We demonstrate the formation of charged molecular packets and their transport within optically created electrical force-field traps in a pH-buffered electrolyte. We call this process photoelectrophoretic localization and transport (PELT). The electrolyte is in contact with a photoconductive semiconductor electrode and a counterelectrode that are connected through an external circuit. A light beam directed to coordinates on the photoconductive electrode surface produces a photocurrent within the circuit and electrolyte. Within the electrolyte, the photocurrent creates localized force-field traps centered at the illuminated coordinates. Charged molecules, including polypeptides and proteins, electrophoretically accumulate into the traps and subsequently can be transported in the electrolyte by moving the traps over the photoconductive electrode in response to movement of the light beam. The molecules in a single trap can be divided into aliquots, and the aliquots can be directed along multiple routes simultaneously by using multiple light beams. This photoelectrophoretic transport of charged molecules by PELT resembles the electrostatic transport of electrons within force-field wells of solid-state charge-coupled devices. The molecules, however, travel in a liquid electrolyte rather than a solid. Furthermore, we have used PELT to position amphoteric biomolecules in three dimensions. A 3D pH gradient was created in an electrolyte medium by controlling the illumination position on a photoconductive anode where protons were generated electrolytically. Photoelectrophoretic transport of amphoteric molecules through the pH gradient resulted in accumulation of the molecules at their apparent 3D isoelectric coordinates in the medium. PMID:16618926

  10. A generalized operational formula based on total electronic densities to obtain 3D pictures of the dual descriptor to reveal nucleophilic and electrophilic sites accurately on closed-shell molecules.

    PubMed

    Martínez-Araya, Jorge I

    2016-09-30

    By means of the conceptual density functional theory, the so-called dual descriptor (DD) has been adapted to be used in any closed-shell molecule that presents degeneracy in its frontier molecular orbitals. The latter is of paramount importance because a correct description of local reactivity will allow to predict the most favorable sites on a molecule to undergo nucleophilic or electrophilic attacks; on the contrary, an incomplete description of local reactivity might have serio us consequences, particularly for those experimental chemists that have the need of getting an insight about reactivity of chemical reagents before using them in synthesis to obtain a new compound. In the present work, the old approach based only on electronic densities of frontier molecular orbitals is replaced by the most accurate procedure that implies the use of total electronic densities thus keeping consistency with the essential principle of the DFT in which the electronic density is the fundamental variable and not the molecular orbitals. As a result of the present work, the DD will be able to properly describe local reactivities only in terms of total electronic densities. To test the proposed operational formula, 12 very common molecules were selected as the original definition of the DD was not able to describe their local reactivities properly. The ethylene molecule was additionally used to test the capability of the proposed operational formula to reveal a correct local reactivity even in absence of degeneracy in frontier molecular orbitals. © 2016 Wiley Periodicals, Inc.

  11. Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking.

    PubMed

    Shaw, Craig D; Storek, Michael J; Young, Kendra A; Kovacs, James M; Thurman, Joshua M; Holers, V Michael; Hannan, Jonathan P

    2010-12-10

    The interactions between the complement receptor type 2 (CR2) and the C3 complement fragments C3d, C3dg, and iC3b are essential for the initiation of a normal immune response. A crystal-derived structure of the two N-terminal short consensus repeat (SCR1-2) domains of CR2 in complex with C3d has previously been elucidated. However, a number of biochemical and biophysical studies targeting both CR2 and C3d appear to be in conflict with these structural data. Previous mutagenesis and heteronuclear NMR spectroscopy studies directed toward the C3d-binding site on CR2 have indicated that the CR2-C3d cocrystal structure may represent an encounter/intermediate or nonphysiological complex. With regard to the CR2-binding site on C3d, mutagenesis studies by Isenman and coworkers [Isenman, D. E., Leung, E., Mackay, J. D., Bagby, S. & van den Elsen, J. M. H. (2010). Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: Implications for the controversy regarding the CR2/C3d cocrystal structure. J. Immunol. 184, 1946-1955] have implicated an electronegative "concave" surface on C3d in the binding process. This surface is discrete from the CR2-C3d interface identified in the crystal structure. We generated a total of 18 mutations targeting the two (X-ray crystallographic- and mutagenesis-based) proposed CR2 SCR1-2 binding sites on C3d. Using ELISA analyses, we were able to assess binding of mutant forms of C3d to CR2. Mutations directed toward the concave surface of C3d result in substantially compromised CR2 binding. By contrast, targeting the CR2-C3d interface identified in the cocrystal structure and the surrounding area results in significantly lower levels of disruption in binding. Molecular modeling approaches used to investigate disparities between the biochemical data and the X-ray structure of the CR2-C3d cocrystal result in highest-scoring solutions in which CR2 SCR1-2 is

  12. The integration of 3-D cell printing and mesoscopic fluorescence molecular tomography of vascular constructs within thick hydrogel scaffolds.

    PubMed

    Zhao, Lingling; Lee, Vivian K; Yoo, Seung-Schik; Dai, Guohao; Intes, Xavier

    2012-07-01

    Developing methods that provide adequate vascular perfusion is an important step toward engineering large functional tissues. Meanwhile, an imaging modality to assess the three-dimensional (3-D) structures and functions of the vascular channels is lacking for thick matrices (>2 ≈ 3 mm). Herein, we report on an original approach to construct and image 3-D dynamically perfused vascular structures in thick hydrogel scaffolds. In this work, we integrated a robotic 3-D cell printing technology with a mesoscopic fluorescence molecular tomography imaging system, and demonstrated the capability of the platform to construct perfused collagen scaffolds with endothelial lining and to image both the fluid flow and fluorescent-labeled living endothelial cells at high-frame rates, with high sensitivity and accuracy. These results establish the potential of integrating both 3-D cell printing and fluorescence mesoscopic imaging for functional and molecular studies in complex tissue-engineered tissues.

  13. 3D-QSAR, molecular docking and molecular dynamics studies of a series of RORγt inhibitors.

    PubMed

    Wang, Fangfang; Yang, Wei; Shi, Yonghui; Le, Guowei

    2015-09-01

    The discovery of clinically relevant inhibitors of retinoic acid receptor-related orphan receptor-gamma-t (RORγt) for autoimmune diseases therapy has proven to be a challenging task. In the present work, to find out the structural features required for the inhibitory activity, we show for the first time a three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulations for a series of novel thiazole/thiophene ketone amides with inhibitory activity at the RORγt receptor. The optimum CoMFA and CoMSIA models, derived from ligand-based superimposition I, exhibit leave-one-out cross-validated correlation coefficient (R(2)cv) of .859 and .805, respectively. Furthermore, the external predictive abilities of the models were evaluated by a test set, producing the predicted correlation coefficient (R(2)pred) of .7317 and .7097, respectively. In addition, molecular docking analysis was applied to explore the binding modes between the inhibitors and the receptor. MD simulation and MM/PBSA method were also employed to study the stability and rationality of the derived conformations, and the binding free energies in detail. The QSAR models and the results of molecular docking, MD simulation, binding free energies corroborate well with each other and further provide insights regarding the development of novel RORγt inhibitors with better activity.

  14. The 3D Structure of the Binding Pocket of the Human Oxytocin Receptor for Benzoxazine Antagonists, Determined by Molecular Docking, Scoring Functions and 3D-QSAR Methods

    NASA Astrophysics Data System (ADS)

    Jójárt, Balázs; Martinek, Tamás A.; Márki, Árpád

    2005-05-01

    Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. These structures were refined by using constrained simulated annealing, and the further ligands were aligned in the refined receptor by molecular docking. A good correlation was found between the estimated Δ G bind and the p K i values for complex F. The Connolly-surface analysis, CoMFA and CoMSIA models q CoMFA 2 = 0.653, q CoMSA 2 = 0.630 and r pred,CoMFA 2 = 0.852 , r pred,CoMSIA 2 = 0.815) confirmed the scoring function results. The structural features of the receptor-ligand complex and the CoMFA and CoMSIA fields are in closely connected. These results suggest that receptor-ligand complex F is the most likely binding hypothesis for the studied benzoxazine analogs.

  15. Anabolic and androgenic activities of 19-nor-testosterone steroids: QSAR study using quantum and physicochemical molecular descriptors.

    PubMed

    Alvarez-Ginarte, Yoanna María; Montero-Cabrera, Luis Alberto; de la Vega, José Manuel García; Noheda-Marín, Pedro; Marrero-Ponce, Yovani; Ruíz-García, José Alberto

    2011-08-01

    Quantitative structure-activity relationship (QSAR) study of 19-nor-testosterone steroids family was performed using quantum and physicochemical molecular descriptors. The quantum-chemical descriptors were calculated using semiempirical calculations. The descriptor values were statistically correlated using multi-linear regression analysis. The QSAR study indicated that the electronic properties of these derivatives have significant relationship with observed biological activities. The found QSAR equations explain that the energy difference between the LUMO and HOMO, the total dipole moment, the chemical potential and the value of the net charge of different carbon atoms in the steroid nucleus showed key interaction of these steroids with their anabolic-androgenic receptor binding site. The calculated values predict that the 17α-cyclopropyl-17β, 3β-hydroxy-4-estrene compound presents the highest anabolic-androgenic ratio (AAR) and the 7α-methyl-17β-acetoxy-estr-4-en-3-one compound the lowest AAR. This study might be helpful in the future successful identification of "real" or "virtual" anabolic-androgenic steroids.

  16. An in-depth spectroscopic examination of molecular bands from 3D hydrodynamical model atmospheres. II. Carbon-enhanced metal-poor 3D model atmospheres

    NASA Astrophysics Data System (ADS)

    Gallagher, A. J.; Caffau, E.; Bonifacio, P.; Ludwig, H.-G.; Steffen, M.; Homeier, D.; Plez, B.

    2017-02-01

    Context. Tighter constraints on metal-poor stars we observe are needed to better understand the chemical processes of the early Universe. Computing a stellar spectrum in 3D allows one to model complex stellar behaviours, which cannot be replicated in 1D. Aims: We examine the effect that the intrinsic CNO abundances have on a 3D model structure and the resulting 3D spectrum synthesis. Methods: Model atmospheres were computed in 3D for three distinct CNO chemical compositions using the CO5BOLD model atmosphere code, and their internal structures were examined. Synthetic spectra were computed from these models using Linfor3D and they were compared. New 3D abundance corrections for the G-band and a selection of UV OH lines were also computed. Results: The varying CNO abundances change the metal content of the 3D models. This had an effect on the model structure and the resulting synthesis. However, it was found that the C/O ratio had a larger effect than the overall metal content of a model. Conclusions: Our results suggest that varying the C/O ratio has a substantial impact on the internal structure of the 3D model, even in the hot turn-off star models explored here. This suggests that bespoke 3D models, for specific CNO abundances should be sought. Such effects are not seen in 1D at these temperature regimes.

  17. Volume-rendering on a 3D hyperwall: A molecular visualization platform for research, education and outreach.

    PubMed

    MacDougall, Preston J; Henze, Christopher E; Volkov, Anatoliy

    2016-11-01

    We present a unique platform for molecular visualization and design that uses novel subatomic feature detection software in tandem with 3D hyperwall visualization technology. We demonstrate the fleshing-out of pharmacophores in drug molecules, as well as reactive sites in catalysts, focusing on subatomic features. Topological analysis with picometer resolution, in conjunction with interactive volume-rendering of the Laplacian of the electronic charge density, leads to new insight into docking and catalysis. Visual data-mining is done efficiently and in parallel using a 4×4 3D hyperwall (a tiled array of 3D monitors driven independently by slave GPUs but displaying high-resolution, synchronized and functionally-related images). The visual texture of images for a wide variety of molecular systems are intuitive to experienced chemists but also appealing to neophytes, making the platform simultaneously useful as a tool for advanced research as well as for pedagogical and STEM education outreach purposes.

  18. Density functional theory fragment descriptors to quantify the reactivity of a molecular family: application to amino acids.

    PubMed

    Senet, P; Aparicio, F

    2007-04-14

    By using the exact density functional theory, one demonstrates that the value of the local electronic softness of a molecular fragment is directly related to the polarization charge (Coulomb hole) induced by a test electron removed (or added) from (at) the fragment. Our finding generalizes to a chemical group a formal relation between these molecular descriptors recently obtained for an atom in a molecule using an approximate atomistic model [P. Senet and M. Yang, J. Chem. Sci. 117, 411 (2005)]. In addition, a practical ab initio computational scheme of the Coulomb hole and related local descriptors of reactivity of a molecular family having in common a similar fragment is presented. As a blind test, the method is applied to the lateral chains of the 20 isolated amino acids. One demonstrates that the local softness of the lateral chain is a quantitative measure of the similarity of the amino acids. It predicts the separation of amino acids in different biochemical groups (aliphatic, basic, acidic, sulfur contained, and aromatic). The present approach may find applications in quantitative structure activity relationship methodology.

  19. Can molecular dynamics simulations help in discriminating correct from erroneous protein 3D models?

    PubMed Central

    Taly, Jean-François; Marin, Antoine; Gibrat, Jean-François

    2008-01-01

    Background Recent approaches for predicting the three-dimensional (3D) structure of proteins such as de novo or fold recognition methods mostly rely on simplified energy potential functions and a reduced representation of the polypeptide chain. These simplifications facilitate the exploration of the protein conformational space but do not permit to capture entirely the subtle relationship that exists between the amino acid sequence and its native structure. It has been proposed that physics-based energy functions together with techniques for sampling the conformational space, e.g., Monte Carlo or molecular dynamics (MD) simulations, are better suited to the task of modelling proteins at higher resolutions than those of models obtained with the former type of methods. In this study we monitor different protein structural properties along MD trajectories to discriminate correct from erroneous models. These models are based on the sequence-structure alignments provided by our fold recognition method, FROST. We define correct models as being built from alignments of sequences with structures similar to their native structures and erroneous models from alignments of sequences with structures unrelated to their native structures. Results For three test sequences whose native structures belong to the all-α, all-β and αβ classes we built a set of models intended to cover the whole spectrum: from a perfect model, i.e., the native structure, to a very poor model, i.e., a random alignment of the test sequence with a structure belonging to another structural class, including several intermediate models based on fold recognition alignments. We submitted these models to 11 ns of MD simulations at three different temperatures. We monitored along the corresponding trajectories the mean of the Root-Mean-Square deviations (RMSd) with respect to the initial conformation, the RMSd fluctuations, the number of conformation clusters, the evolution of secondary structures and the

  20. N-tuple topological/geometric cutoffs for 3D N-linear algebraic molecular codifications: variability, linear independence and QSAR analysis.

    PubMed

    García-Jacas, C R; Marrero-Ponce, Y; Barigye, S J; Hernández-Ortega, T; Cabrera-Leyva, L; Fernández-Castillo, A

    2016-12-01

    Novel N-tuple topological/geometric cutoffs to consider specific inter-atomic relations in the QuBiLS-MIDAS framework are introduced in this manuscript. These molecular cutoffs permit the taking into account of relations between more than two atoms by using (dis-)similarity multi-metrics and the concepts related with topological and Euclidean-geometric distances. To this end, the kth two-, three- and four-tuple topological and geometric neighbourhood quotient (NQ) total (or local-fragment) spatial-(dis)similarity matrices are defined, to represent 3D information corresponding to the relations between two, three and four atoms of the molecular structures that satisfy certain cutoff criteria. First, an analysis of a diverse chemical space for the most common values of topological/Euclidean-geometric distances, bond/dihedral angles, triangle/quadrilateral perimeters, triangle area and volume was performed in order to determine the intervals to take into account in the cutoff procedures. A variability analysis based on Shannon's entropy reveals that better distribution patterns are attained with the descriptors based on the cutoffs proposed (QuBiLS-MIDAS NQ-MDs) with regard to the results obtained when all inter-atomic relations are considered (QuBiLS-MIDAS KA-MDs - 'Keep All'). A principal component analysis shows that the novel molecular cutoffs codify chemical information captured by the respective QuBiLS-MIDAS KA-MDs, as well as information not captured by the latter. Lastly, a QSAR study to obtain deeper knowledge of the contribution of the proposed methods was carried out, using four molecular datasets (steroids (STER), angiotensin converting enzyme (ACE), thermolysin inhibitors (THER) and thrombin inhibitors (THR)) widely used as benchmarks in the evaluation of several methodologies. One to four variable QSAR models based on multiple linear regression were developed for each compound dataset following the original division into training and test sets. The

  1. Molecular dynamics simulations of wild type and mutants of human complement receptor 2 complexed with C3d.

    PubMed

    Wan, Hua; Hu, Jian-ping; Tian, Xu-hong; Chang, Shan

    2013-01-28

    The interaction between human complement receptor type 2 (CR2) and antigen-bound C3d can bridge the innate and adaptive immune systems. The recently determined structure of the CR2(SCR1-2):C3d complex has revealed the expected binding interface of CR2-C3d. In this article, wild type (WT) and three mutants of the new structure are studied by molecular dynamics (MD) simulations. The differently decreased structural stabilities of the mutants relative to WT are shown to be consistent with the experimental data, which can be explained by the different hydrogen bond patterns at the interfaces. It is also found that two clusters of residues (D36/E37/E39 and E160/D163/E166) in the acidic pocket of C3d are important for CR2-C3d interactions, which is in good agreement with previous mutagenesis study. In addition, functional dynamics and the conformational change of CR2 are explored by using domain cross-correlation map (DCCM), principal component analysis (PCA), and free energy landscape (FEL) methods. The conformational change mainly corresponds to the opening of a V-shaped structure of CR2, which is consistent with the previously reported high interdomain flexibility of CR2. We further suppose that the opening of a V-shaped structure of CR2 may favor the binding stability of CR2(SCR1-2):C3d. This study would provide some new insights into the understanding of the CR2-C3d interaction mechanism.

  2. Determination of 3D molecular orientation by concurrent polarization analysis of multiple Raman modes in broadband CARS spectroscopy

    PubMed Central

    2016-01-01

    A theoretical description is presented about a new analysis method to determine three-dimensional (3D) molecular orientation by concurrently analyzing multiple Raman polarization profiles. Conventional approaches to polarization Raman spectroscopy are based on single peaks, and their 2D-projected polarization profiles are limited in providing 3D orientational information. Our new method analyzes multiple Raman profiles acquired by a single polarization scanning measurement of broadband coherent anti-Stokes Raman scattering (BCARS). Because the analysis uses only dimensionless quantities, such as intensity ratios and phase difference between multiple profiles, the results are not affected by sample concentration and the system response function. We describe how to determine the 3D molecular orientation with the dimensionless observables by using two simplified model cases. In addition, we discuss the effect of orientational broadening on the polarization profiles in the two model cases. We find that in the presence of broadening we can still determine the mean 3D orientation angles and, furthermore, the degree of orientational broadening. PMID:26561197

  3. Non-Newtonian models for molecular viscosity and wall shear stress in a 3D reconstructed human left coronary artery.

    PubMed

    Soulis, Johannes V; Giannoglou, George D; Chatzizisis, Yiannis S; Seralidou, Kypriani V; Parcharidis, George E; Louridas, George E

    2008-01-01

    The capabilities and limitations of various molecular viscosity models, in the left coronary arterial tree, were analyzed via: molecular viscosity, local and global non-Newtonian importance factors, wall shear stress (WSS) and wall shear stress gradient (WSSG). The vessel geometry was acquired using geometrically correct 3D intravascular ultrasound (3D IVUS). Seven non-Newtonian molecular viscosity models, plus the Newtonian one, were compared. The WSS distribution yielded a consistent LCA pattern for nearly all non-Newtonian models. High molecular viscosity, low WSS and low WSSG values occurred at the outer walls of the major bifurcation in proximal LCA regions. The Newtonian blood flow was found to be a good approximation at mid- and high-strain rates. The non-Newtonian Power Law, Generalized Power Law, Carreau and Casson and Modified Cross blood viscosity models gave comparable molecular viscosity, WSS and WSSG values. The Power Law and Walburn-Schneck models over-estimated the non-Newtonian global importance factor I(G) and under-estimated the area averaged WSS and WSSG values. The non-Newtonian Power Law and the Generalized Power Law blood viscosity models were found to approximate the molecular viscosity and WSS calculations in a more satisfactory way.

  4. QuBiLS-MIDAS: a parallel free-software for molecular descriptors computation based on multilinear algebraic maps.

    PubMed

    García-Jacas, César R; Marrero-Ponce, Yovani; Acevedo-Martínez, Liesner; Barigye, Stephen J; Valdés-Martiní, José R; Contreras-Torres, Ernesto

    2014-07-05

    The present report introduces the QuBiLS-MIDAS software belonging to the ToMoCoMD-CARDD suite for the calculation of three-dimensional molecular descriptors (MDs) based on the two-linear (bilinear), three-linear, and four-linear (multilinear or N-linear) algebraic forms. Thus, it is unique software that computes these tensor-based indices. These descriptors, establish relations for two, three, and four atoms by using several (dis-)similarity metrics or multimetrics, matrix transformations, cutoffs, local calculations and aggregation operators. The theoretical background of these N-linear indices is also presented. The QuBiLS-MIDAS software was developed in the Java programming language and employs the Chemical Development Kit library for the manipulation of the chemical structures and the calculation of the atomic properties. This software is composed by a desktop user-friendly interface and an Abstract Programming Interface library. The former was created to simplify the configuration of the different options of the MDs, whereas the library was designed to allow its easy integration to other software for chemoinformatics applications. This program provides functionalities for data cleaning tasks and for batch processing of the molecular indices. In addition, it offers parallel calculation of the MDs through the use of all available processors in current computers. The studies of complexity of the main algorithms demonstrate that these were efficiently implemented with respect to their trivial implementation. Lastly, the performance tests reveal that this software has a suitable behavior when the amount of processors is increased. Therefore, the QuBiLS-MIDAS software constitutes a useful application for the computation of the molecular indices based on N-linear algebraic maps and it can be used freely to perform chemoinformatics studies.

  5. Octanol-Water Partition Coefficient from 3D-RISM-KH Molecular Theory of Solvation with Partial Molar Volume Correction.

    PubMed

    Huang, WenJuan; Blinov, Nikolay; Kovalenko, Andriy

    2015-04-30

    The octanol-water partition coefficient is an important physical-chemical characteristic widely used to describe hydrophobic/hydrophilic properties of chemical compounds. The partition coefficient is related to the transfer free energy of a compound from water to octanol. Here, we introduce a new protocol for prediction of the partition coefficient based on the statistical-mechanical, 3D-RISM-KH molecular theory of solvation. It was shown recently that with the compound-solvent correlation functions obtained from the 3D-RISM-KH molecular theory of solvation, the free energy functional supplemented with the correction linearly related to the partial molar volume obtained from the Kirkwood-Buff/3D-RISM theory, also called the "universal correction" (UC), provides accurate prediction of the hydration free energy of small compounds, compared to explicit solvent molecular dynamics [ Palmer , D. S. ; J. Phys.: Condens. Matter 2010 , 22 , 492101 ]. Here we report that with the UC reparametrized accordingly this theory also provides an excellent agreement with the experimental data for the solvation free energy in nonpolar solvent (1-octanol) and so accurately predicts the octanol-water partition coefficient. The performance of the Kovalenko-Hirata (KH) and Gaussian fluctuation (GF) functionals of the solvation free energy, with and without UC, is tested on a large library of small compounds with diverse functional groups. The best agreement with the experimental data for octanol-water partition coefficients is obtained with the KH-UC solvation free energy functional.

  6. Low-Cost 3D Printers Enable High-Quality and Automated Sample Preparation and Molecular Detection.

    PubMed

    Chan, Kamfai; Coen, Mauricio; Hardick, Justin; Gaydos, Charlotte A; Wong, Kah-Yat; Smith, Clayton; Wilson, Scott A; Vayugundla, Siva Praneeth; Wong, Season

    2016-01-01

    Most molecular diagnostic assays require upfront sample preparation steps to isolate the target's nucleic acids, followed by its amplification and detection using various nucleic acid amplification techniques. Because molecular diagnostic methods are generally rather difficult to perform manually without highly trained users, automated and integrated systems are highly desirable but too costly for use at point-of-care or low-resource settings. Here, we showcase the development of a low-cost and rapid nucleic acid isolation and amplification platform by modifying entry-level 3D printers that cost between $400 and $750. Our modifications consisted of replacing the extruder with a tip-comb attachment that houses magnets to conduct magnetic particle-based nucleic acid extraction. We then programmed the 3D printer to conduct motions that can perform high-quality extraction protocols. Up to 12 samples can be processed simultaneously in under 13 minutes and the efficiency of nucleic acid isolation matches well against gold-standard spin-column-based extraction technology. Additionally, we used the 3D printer's heated bed to supply heat to perform water bath-based polymerase chain reactions (PCRs). Using another attachment to hold PCR tubes, the 3D printer was programmed to automate the process of shuttling PCR tubes between water baths. By eliminating the temperature ramping needed in most commercial thermal cyclers, the run time of a 35-cycle PCR protocol was shortened by 33%. This article demonstrates that for applications in resource-limited settings, expensive nucleic acid extraction devices and thermal cyclers that are used in many central laboratories can be potentially replaced by a device modified from inexpensive entry-level 3D printers.

  7. Low-Cost 3D Printers Enable High-Quality and Automated Sample Preparation and Molecular Detection

    PubMed Central

    Chan, Kamfai; Coen, Mauricio; Hardick, Justin; Gaydos, Charlotte A.; Wong, Kah-Yat; Smith, Clayton; Wilson, Scott A.; Vayugundla, Siva Praneeth; Wong, Season

    2016-01-01

    Most molecular diagnostic assays require upfront sample preparation steps to isolate the target’s nucleic acids, followed by its amplification and detection using various nucleic acid amplification techniques. Because molecular diagnostic methods are generally rather difficult to perform manually without highly trained users, automated and integrated systems are highly desirable but too costly for use at point-of-care or low-resource settings. Here, we showcase the development of a low-cost and rapid nucleic acid isolation and amplification platform by modifying entry-level 3D printers that cost between $400 and $750. Our modifications consisted of replacing the extruder with a tip-comb attachment that houses magnets to conduct magnetic particle-based nucleic acid extraction. We then programmed the 3D printer to conduct motions that can perform high-quality extraction protocols. Up to 12 samples can be processed simultaneously in under 13 minutes and the efficiency of nucleic acid isolation matches well against gold-standard spin-column-based extraction technology. Additionally, we used the 3D printer’s heated bed to supply heat to perform water bath-based polymerase chain reactions (PCRs). Using another attachment to hold PCR tubes, the 3D printer was programmed to automate the process of shuttling PCR tubes between water baths. By eliminating the temperature ramping needed in most commercial thermal cyclers, the run time of a 35-cycle PCR protocol was shortened by 33%. This article demonstrates that for applications in resource-limited settings, expensive nucleic acid extraction devices and thermal cyclers that are used in many central laboratories can be potentially replaced by a device modified from inexpensive entry-level 3D printers. PMID:27362424

  8. PEA-CLARITY: 3D molecular imaging of whole plant organs

    PubMed Central

    Palmer, William M.; Martin, Antony P.; Flynn, Jamie R.; Reed, Stephanie L.; White, Rosemary G.; Furbank, Robert T.; Grof, Christopher P. L.

    2015-01-01

    Here we report the adaptation of the CLARITY technique to plant tissues with addition of enzymatic degradation to improve optical clearing and facilitate antibody probe penetration. Plant-Enzyme-Assisted (PEA)-CLARITY, has allowed deep optical visualisation of stains, expressed fluorescent proteins and IgG-antibodies in Tobacco and Arabidopsis leaves. Enzyme treatment enabled penetration of antibodies into whole tissues without the need for any sectioning of the material, thus facilitating protein localisation of intact tissue in 3D whilst retaining cellular structure. PMID:26328508

  9. Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis

    SciTech Connect

    Lambros, Maria Polikandritou; Parsa, Cyrus; Mulamalla, HariChandana; Orlando, Robert; Lau, Bernard; Huang, Ying; Pon, Doreen; Chow, Moses

    2011-02-04

    Research highlights: {yields} We irradiated a 3-D human oral cell culture of keratinocytes and fibroblasts with 12 and 2 Gy. {yields} 6 h after irradiation the histopathology and apoptosis of the 3-D culture were evaluated. Microarrays were used to assess the gene expression in the irradiated 3-D tissue. {yields} 12 Gy induced significant histopathologic changes and cellular apoptosis. {yields} 12 Gy significantly affected genes of the NF-kB pathway, inflammatory cytokines and DAMPs. -- Abstract: Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this

  10. Modulating mechanical behaviour of 3D-printed cartilage-mimetic PCL scaffolds: influence of molecular weight and pore geometry.

    PubMed

    Olubamiji, Adeola D; Izadifar, Zohreh; Si, Jennifer L; Cooper, David M L; Eames, B Frank; Chen, Daniel X B

    2016-06-22

    Three-dimensional (3D)-printed poly(ε)-caprolactone (PCL)-based scaffolds are increasingly being explored for cartilage tissue engineering (CTE) applications. However, ensuring that the mechanical properties of these PCL-based constructs are comparable to that of articular cartilage that they are meant to regenerate is an area that has been under-explored. This paper presents the effects of PCL's molecular weight (MW) and scaffold's pore geometric configurations; strand size (SZ), strand spacing (SS), and strand orientation (SO), on mechanical properties of 3D-printed PCL scaffolds. The results illustrate that MW has significant effect on compressive moduli and yield strength of 3D-printed PCL scaffolds. Specifically, PCL with MW of 45 K was a more feasible choice for fabrication of visco-elastic, flexible and load-bearing PCL scaffolds. Furthermore, pore geometric configurations; SZ, SS, and SO, all significantly affect on tensile moduli of scaffolds. However, only SZ and SS have statistically significant effects on compressive moduli and porosity of these scaffolds. That said, inverse linear relationship was observed between porosity and mechanical properties of 3D-printed PCL scaffolds in Pearson's correlation test. Altogether, this study illustrates that modulating MW of PCL and pore geometrical configurations of the scaffolds enabled design and fabrication of PCL scaffolds with mechanical and biomimetic properties that better mimic mechanical behaviour of human articular cartilage. Thus, the modulated PCL scaffold proposed in this study is a framework that offers great potentials for CTE applications.

  11. [MOLECULAR EVOLUTION OF ION CHANNELS: AMINO ACID SEQUENCES AND 3D STRUCTURES].

    PubMed

    Korkosh, V S; Zhorov, B S; Tikhonov, D B

    2016-01-01

    An integral part of modern evolutionary biology is comparative analysis of structure and function of macromolecules such as proteins. The first and critical step to understand evolution of homologous proteins is their amino acid sequence alignment. However, standard algorithms fop not provide unambiguous sequence alignments for proteins of poor homology. More reliable results can be obtained by comparing experimental 3D structures obtained at atomic resolution, for instance, with the aid of X-ray structural analysis. If such structures are lacking, homology modeling is used, which may take into account indirect experimental data on functional roles of individual amino-acid residues. An important problem is that the sequence alignment, which reflects genetic modifications, does not necessarily correspond to the functional homology. The latter depends on three-dimensional structures which are critical for natural selection. Since alignment techniques relying only on the analysis of primary structures carry no information on the functional properties of proteins, including 3D structures into consideration is very important. Here we consider several examples involving ion channels and demonstrate that alignment of their three-dimensional structures can significantly improve sequence alignments obtained by traditional methods.

  12. Molecular Phylogeny and Predicted 3D Structure of Plant beta-D-N-Acetylhexosaminidase

    PubMed Central

    Hossain, Md. Anowar

    2014-01-01

    beta-D-N-Acetylhexosaminidase, a family 20 glycosyl hydrolase, catalyzes the removal of β-1,4-linked N-acetylhexosamine residues from oligosaccharides and their conjugates. We constructed phylogenetic tree of β-hexosaminidases to analyze the evolutionary history and predicted functions of plant hexosaminidases. Phylogenetic analysis reveals the complex history of evolution of plant β-hexosaminidase that can be described by gene duplication events. The 3D structure of tomato β-hexosaminidase (β-Hex-Sl) was predicted by homology modeling using 1now as a template. Structural conformity studies of the best fit model showed that more than 98% of the residues lie inside the favoured and allowed regions where only 0.9% lie in the unfavourable region. Predicted 3D structure contains 531 amino acids residues with glycosyl hydrolase20b domain-I and glycosyl hydrolase20 superfamily domain-II including the (β/α)8 barrel in the central part. The α and β contents of the modeled structure were found to be 33.3% and 12.2%, respectively. Eleven amino acids were found to be involved in ligand-binding site; Asp(330) and Glu(331) could play important roles in enzyme-catalyzed reactions. The predicted model provides a structural framework that can act as a guide to develop a hypothesis for β-Hex-Sl mutagenesis experiments for exploring the functions of this class of enzymes in plant kingdom. PMID:25165734

  13. A Molecular Perspective of Inter-filament Bonding in Fused Deposition Modeling 3-D Printing

    NASA Astrophysics Data System (ADS)

    Duranty, Edward; Spradlin, Brandon; Dadmun, Mark

    2015-03-01

    Fused deposition 3D printing is an important tool for low-cost and rapid prototyping of objects with complex geometries. 3D printed materials are composed of many filaments deposited on a heated substrate, requiring the bonding of neighboring filaments during the deposition process. Filament deposition often creates voids between filaments, which requires necking between them to create a robust sample. Therefore the amount of interfacial contact and interdiffusion between filaments become important parameters that control the macroscopic physical properties of the printed prototype. Our research focuses on quantifying the interfacial adhesion between ABS filaments and its impact on structural properties. The time evolution of the temperature profile near the heated substrate demonstrates that the deposited filaments are repeatedly heated above the Tg of ABS allowing interpenetration of the polymer chains between adjacent filaments. Results of DMA experiments on samples of different geometries have been correlated to microphotography that monitors the degree of necking between filaments and the thermal history. Results indicate that interfacial contact area between filaments and increased thermal energy are crucial to their mechanical properties.

  14. Molecular phylogeny and predicted 3D structure of plant beta-D-N-acetylhexosaminidase.

    PubMed

    Hossain, Md Anowar; Roslan, Hairul Azman

    2014-01-01

    beta-D-N-Acetylhexosaminidase, a family 20 glycosyl hydrolase, catalyzes the removal of β-1,4-linked N-acetylhexosamine residues from oligosaccharides and their conjugates. We constructed phylogenetic tree of β-hexosaminidases to analyze the evolutionary history and predicted functions of plant hexosaminidases. Phylogenetic analysis reveals the complex history of evolution of plant β-hexosaminidase that can be described by gene duplication events. The 3D structure of tomato β-hexosaminidase (β-Hex-Sl) was predicted by homology modeling using 1now as a template. Structural conformity studies of the best fit model showed that more than 98% of the residues lie inside the favoured and allowed regions where only 0.9% lie in the unfavourable region. Predicted 3D structure contains 531 amino acids residues with glycosyl hydrolase20b domain-I and glycosyl hydrolase20 superfamily domain-II including the (β/α)8 barrel in the central part. The α and β contents of the modeled structure were found to be 33.3% and 12.2%, respectively. Eleven amino acids were found to be involved in ligand-binding site; Asp(330) and Glu(331) could play important roles in enzyme-catalyzed reactions. The predicted model provides a structural framework that can act as a guide to develop a hypothesis for β-Hex-Sl mutagenesis experiments for exploring the functions of this class of enzymes in plant kingdom.

  15. Electrospray Ionization Efficiency Is Dependent on Different Molecular Descriptors with Respect to Solvent pH and Instrumental Configuration

    PubMed Central

    Kiontke, Andreas; Oliveira-Birkmeier, Ariana; Opitz, Andreas

    2016-01-01

    Over the past decades, electrospray ionization for mass spectrometry (ESI-MS) has become one of the most commonly employed techniques in analytical chemistry, mainly due to its broad applicability to polar and semipolar compounds and the superior selectivity which is achieved in combination with high resolution separation techniques. However, responsiveness of an analytical method also determines its suitability for the quantitation of chemical compounds; and in electrospray ionization for mass spectrometry, it can vary significantly among different analytes with identical solution concentrations. Therefore, we investigated the ESI-response behavior of 56 nitrogen-containing compounds including aromatic amines and pyridines, two compound classes of high importance to both, synthetic organic chemistry as well as to pharmaceutical sciences. These compounds are increasingly analyzed employing ESI mass spectrometry detection due to their polar, basic character. Signal intensities of the peaks from the protonated molecular ion (MH+) were acquired under different conditions and related to compound properties such as basicity, polarity, volatility and molecular size exploring their quantitative impact on ionization efficiency. As a result, we found that though solution basicity of a compound is the main factor initially determining the ESI response of the protonated molecular ion, other factors such as polarity and vaporability become more important under acidic solvent conditions and may nearly outweigh the importance of basicity under these conditions. Moreover, we show that different molecular descriptors may become important when using different types of instruments for such investigations, a fact not detailed so far in the available literature. PMID:27907110

  16. Combining and comparing morphometric shape descriptors with a molecular phylogeny: the case of fruit type evolution in Bornean Lithocarpus (Fagaceae).

    PubMed

    Cannon, C H; Manos, P S

    2001-01-01

    Fruit type in the genus Lithocarpus (Fagaceae) includes both classic oak acorns and novel modifications. Bornean taxa with modified fruits can be separated into two sections (Synaedrys and Lithocarpus) based on subtle shape differences. By following strict criteria for homology and representation, this variation in shape can be captured and the sections distinguished by using elliptic Fourier or eigenshape analysis. Phenograms of fruit shape, constructed by using restricted maximum likelihood techniques and these morphometric descriptors, were incorporated into combined and comparative analyses with molecular sequence data from the internal transcribed spacer (ITS) region of the nuclear rDNA, using branch-weighted matrix representation. The combined analysis strongly suggested independent derivation of the novel fruit type in the two sections from different acornlike ancestors, while the comparative analysis indicated frequent decoupling between the molecular and morphological changes as inferred at well-supported nodes. The acorn fruit type has undergone little modification between ingroup and outgroup, despite large molecular distance. Greater morphological than molecular change was inferred at critical transitions between acorn and novel fruit types, particularly for section Lithocarpus. The combination of these two different types of data improved our understanding of the macroevolution of fruit type in this difficult group, and the comparative analysis highlighted the significant incongruities in evolutionary pattern between the two datasets.

  17. From 3D to 2D: A Review of the Molecular Imprinting of Proteins

    PubMed Central

    Turner, Nicholas W.; Jeans, Christopher W.; Brain, Keith R.; Allender, Christopher J.; Hlady, Vladimir; Britt, David W.

    2008-01-01

    Molecular imprinting is a generic technology that allows for the introduction of sites of specific molecular affinity into otherwise homogeneous polymeric matrices. Commonly this technique has been shown to be effective when targeting small molecules of molecular weight <1500, while extending the technique to larger molecules such as proteins has proven difficult. A number of key inherent problems in protein imprinting have been identified, including permanent entrapment, poor mass transfer, denaturation, and heterogeneity in binding pocket affinity, which have been addressed using a variety of approaches. This review focuses on protein imprinting in its various forms, ranging from conventional bulk techniques to novel thin film and monolayer surface imprinting approaches. PMID:17137293

  18. Cryptic Species in Tropic Sands - Interactive 3D Anatomy, Molecular Phylogeny and Evolution of Meiofaunal Pseudunelidae (Gastropoda, Acochlidia)

    PubMed Central

    Neusser, Timea P.; Jörger, Katharina M.; Schrödl, Michael

    2011-01-01

    Background Towards realistic estimations of the diversity of marine animals, tiny meiofaunal species usually are underrepresented. Since the biological species concept is hardly applicable on exotic and elusive animals, it is even more important to apply a morphospecies concept on the best level of information possible, using accurate and efficient methodology such as 3D modelling from histological sections. Molecular approaches such as sequence analyses may reveal further, cryptic species. This is the first case study on meiofaunal gastropods to test diversity estimations from traditional taxonomy against results from modern microanatomical methodology and molecular systematics. Results The examined meiofaunal Pseudunela specimens from several Indo-Pacific islands cannot be distinguished by external features. Their 3D microanatomy shows differences in the organ systems and allows for taxonomic separation in some cases. Additional molecular analyses based on partial mitochondrial cytochrome c oxidase subunit I (COI) and 16S rRNA markers revealed considerable genetic structure that is largely congruent with anatomical or geographical patterns. Two new species (Pseudunela viatoris and P. marteli spp. nov.) are formally described integrating morphological and genetic analyses. Phylogenetic analysis using partial 16S rRNA, COI and the nuclear 18S rRNA markers shows a clade of Pseudunelidae species as the sister group to limnic Acochlidiidae. Within Pseudunela, two subtypes of complex excretory systems occur. A complex kidney already evolved in the ancestor of Hedylopsacea. Several habitat shifts occurred during hedylopsacean evolution. Conclusions Cryptic species occur in tropical meiofaunal Pseudunela gastropods, and likely in other meiofaunal groups with poor dispersal abilities, boosting current diversity estimations. Only a combined 3D microanatomical and molecular approach revealed actual species diversity within Pseudunela reliably. Such integrative methods are

  19. Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis.

    PubMed

    Lambros, Maria Polikandritou; Parsa, Cyrus; Mulamalla, HariChandana; Orlando, Robert; Lau, Bernard; Huang, Ying; Pon, Doreen; Chow, Moses

    2011-02-04

    Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this is an important first step towards the development 3-D tissue as a screening tool.

  20. Alignment-independent technique for 3D QSAR analysis.

    PubMed

    Wilkes, Jon G; Stoyanova-Slavova, Iva B; Buzatu, Dan A

    2016-04-01

    Molecular biochemistry is controlled by 3D phenomena but structure-activity models based on 3D descriptors are infrequently used for large data sets because of the computational overhead for determining molecular conformations. A diverse dataset of 146 androgen receptor binders was used to investigate how different methods for defining molecular conformations affect the performance of 3D-quantitative spectral data activity relationship models. Molecular conformations tested: (1) global minimum of molecules' potential energy surface; (2) alignment-to-templates using equal electronic and steric force field contributions; (3) alignment using contributions "Best-for-Each" template; (4) non-energy optimized, non-aligned (2D > 3D). Aggregate predictions from models were compared. Highest average coefficients of determination ranged from R Test (2) = 0.56 to 0.61. The best model using 2D > 3D (imported directly from ChemSpider) produced R Test (2) = 0.61. It was superior to energy-minimized and conformation-aligned models and was achieved in only 3-7 % of the time required using the other conformation strategies. Predictions averaged from models built on different conformations achieved a consensus R Test (2) = 0.65. The best 2D > 3D model was analyzed for underlying structure-activity relationships. For the compound strongest binding to the androgen receptor, 10 substructural features contributing to binding were flagged. Utility of 2D > 3D was compared for two other activity endpoints, each modeling a medium sized data set. Results suggested that large scale, accurate predictions using 2D > 3D SDAR descriptors may be produced for interactions involving endocrine system nuclear receptors and other data sets in which strongest activities are produced by fairly inflexible substrates.

  1. Alignment-independent technique for 3D QSAR analysis

    NASA Astrophysics Data System (ADS)

    Wilkes, Jon G.; Stoyanova-Slavova, Iva B.; Buzatu, Dan A.

    2016-04-01

    Molecular biochemistry is controlled by 3D phenomena but structure-activity models based on 3D descriptors are infrequently used for large data sets because of the computational overhead for determining molecular conformations. A diverse dataset of 146 androgen receptor binders was used to investigate how different methods for defining molecular conformations affect the performance of 3D-quantitative spectral data activity relationship models. Molecular conformations tested: (1) global minimum of molecules' potential energy surface; (2) alignment-to-templates using equal electronic and steric force field contributions; (3) alignment using contributions "Best-for-Each" template; (4) non-energy optimized, non-aligned (2D > 3D). Aggregate predictions from models were compared. Highest average coefficients of determination ranged from R Test 2 = 0.56 to 0.61. The best model using 2D > 3D (imported directly from ChemSpider) produced R Test 2 = 0.61. It was superior to energy-minimized and conformation-aligned models and was achieved in only 3-7 % of the time required using the other conformation strategies. Predictions averaged from models built on different conformations achieved a consensus R Test 2 = 0.65. The best 2D > 3D model was analyzed for underlying structure-activity relationships. For the compound strongest binding to the androgen receptor, 10 substructural features contributing to binding were flagged. Utility of 2D > 3D was compared for two other activity endpoints, each modeling a medium sized data set. Results suggested that large scale, accurate predictions using 2D > 3D SDAR descriptors may be produced for interactions involving endocrine system nuclear receptors and other data sets in which strongest activities are produced by fairly inflexible substrates.

  2. Convergent study of Ru-ligand interactions through QTAIM, ELF, NBO molecular descriptors and TDDFT analysis of organometallic dyes

    NASA Astrophysics Data System (ADS)

    Sánchez-Coronilla, Antonio; Sánchez-Márquez, Jesús; Zorrilla, David; Martín, Elisa I.; de los Santos, Desireé M.; Navas, Javier; Fernández-Lorenzo, Concha; Alcántara, Rodrigo; Martín-Calleja, Joaquín

    2014-08-01

    We report a theoretical study of a series of Ru complexes of interest in dye-sensitised solar cells, in organic light-emitting diodes, and in the war against cancer. Other metal centres, such as Cr, Co, Ni, Rh, Pd, and Pt, have been included for comparison purposes. The metal-ligand trends in organometallic chemistry for those compounds are shown synergistically by using three molecular descriptors: quantum theory of atoms in molecules (QTAIM), electron localisation function (ELF) and second-order perturbation theory analysis of the natural bond orbital (NBO). The metal-ligand bond order is addressed through both delocalisation index (DI) of QTAIM and fluctuation index (λ) of ELF. Correlation between DI and λ for Ru-N bond in those complexes is introduced for the first time. Electron transfer and stability was also assessed by the second-order perturbation theory analysis of the NBO. Electron transfer from the lone pair NBO of the ligands toward the antibonding lone pair NBO of the metal plays a relevant role in stabilising the complexes, providing useful insights into understanding the effect of the 'expanded ligand' principle in supramolecular chemistry. Finally, absorption wavelengths associated to the metal-to-ligand charge transfer transitions and the highest occupied molecular orbital (HOMO)--lowest unoccupied molecular orbital (LUMO) characteristics were studied by time-dependent density functional theory.

  3. Synthesis, structure determination and 3D molecular modeling of some novel manganese(II) complexes

    NASA Astrophysics Data System (ADS)

    Hari Kumaran Nair, M. L.; Lalitha, K. P.

    2013-06-01

    Some novel manganese(II) complexes with the ligand (z)-4-((2-hydroxy-4-methoxyphenyl)diazenyl)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one, MPAAP, 3-methoxy phenol azoantipyrine, L1, having the formulae [Mn(L1)2(X)2], [Mn(L1)2(Y)2], where X = Cl- / Br-; Y = NCS- were synthesized and characterized by elemental analysis, molar conductance and magnetic susceptibility measurements, spectral (IR, UV-Visible, EPR, FAB mass) studies, thermogravimetric analysis, powder XRD and cyclic voltammetric studies and by SEM image. An octahedral structure is tentatively proposed for the complexes with respect to the above studies. The [Mn(L1)2(Y)2] was subjected to γ-ray irradiation and the internal changes accompanied were evaluated. The energy minimized configuration of the complex [Mn(L1)2(Y)2] was made with CHEM Bio 3D Ultra 11.0 and the respective parameters are computed. The ligand and its complex [Mn(L1)2(Y)2] were screened for their possible antimicrobial activities.

  4. A structure-activity relationship study of catechol- O-methyltransferase inhibitors combining molecular docking and 3D QSAR methods

    NASA Astrophysics Data System (ADS)

    Tervo, Anu J.; Nyrönen, Tommi H.; Rönkkö, Toni; Poso, Antti

    2003-12-01

    A panel of 92 catechol- O-methyltransferase (COMT) inhibitors was used to examine the molecular interactions affecting their biological activity. COMT inhibitors are used as therapeutic agents in the treatment of Parkinson's disease, but there are limitations in the currently marketed compounds due to adverse side effects. This study combined molecular docking methods with three-dimensional structure-activity relationships (3D QSAR) to analyse possible interactions between COMT and its inhibitors, and to incite the design of new inhibitors. Comparative molecular field analysis (CoMFA) and GRID/GOLPE models were made by using bioactive conformations from docking experiments, which yielded q2 values of 0.594 and 0.636, respectively. The docking results, the COMT X-ray structure, and the 3D QSAR models are in agreement with each other. The models suggest that an interaction between the inhibitor's catechol oxygens and the Mg2+ ion in the COMT active site is important. Both hydrogen bonding with Lys144, Asn170 and Glu199, and hydrophobic contacts with Trp38, Pro174 and Leu198 influence inhibitor binding. Docking suggests that a large R1 substituent of the catechol ring can form hydrophobic contacts with side chains of Val173, Leu198, Met201 and Val203 on the COMT surface. Our models propose that increasing steric volume of e.g. the diethylamine tail of entacapone is favourable for COMT inhibitory activity.

  5. Fast 3D molecular superposition and similarity search in databases of flexible molecules

    NASA Astrophysics Data System (ADS)

    Krämer, Andreas; Horn, Hans W.; Rice, Julia E.

    2003-01-01

    We present a new method (fFLASH) for the virtual screening of compound databases that is based on explicit three-dimensional molecular superpositions. fFLASH takes the torsional flexibility of the database molecules fully into account, and can deal with an arbitrary number of conformation-dependent molecular features. The method utilizes a fragmentation-reassembly approach which allows for an efficient sampling of the conformational space. A fast clique-based pattern matching algorithm generates alignments of pairs of adjacent molecular fragments on the rigid query molecule that are subsequently reassembled to complete database molecules. Using conventional molecular features (hydrogen bond donors and acceptors, charges, and hydrophobic groups) we show that fFLASH is able to rapidly produce accurate alignments of medium-sized drug-like molecules. Experiments with a test database containing a diverse set of 1780 drug-like molecules (including all conformers) have shown that average query processing times of the order of 0.1 seconds per molecule can be achieved on a PC.

  6. Pharmacophore modeling, 3D-QSAR and molecular docking studies of benzimidazole derivatives as potential FXR agonists.

    PubMed

    Sindhu, Thangaraj; Srinivasan, Pappu

    2014-08-01

    Farnesoid X receptor (FXR) is a potential therapeutic target for the treatment of diabetes mellitus. Atom-based three-dimensional quantitative structure activity relationship (3D-QSAR) models were developed for a series of 48 benzimidazole-based agonists of FXR. A total of five pharmacophore hypotheses were generated based on the survival score to build QSAR models. HHHRR was considered as a best model that consisted of three hydrophobic features (H) and two aromatic rings (R). The best hypothesis, HHHRR yielded a 3D-QSAR model with good statistical value (R(2)) of 0.8974 for a training set of 39 compounds and also showed good predictive power with correlation coefficient (Q(2)) of 0.7559 for a test set of nine compounds. Furthermore, molecular docking simulation was performed to understand the binding affinity of 48 benzimidazole-based compounds against the active site of human FXR protein. Docking results revealed that both the most active and least active compounds showed similar binding mode to the experimentally observed binding mode of co-crystallized ligand. The generated 3D contour maps revealed the structure activity relationship of the compounds. Substitution effects at different positions of benzimidazole derivatives would lead to the discovery of new agonists against human FXR protein.

  7. Inhibitory mode of indole-2-carboxamide derivatives against HLGPa: molecular docking and 3D-QSAR analyses.

    PubMed

    Liu, Guixia; Zhang, Zhenshan; Luo, Xiaomin; Shen, Jianhua; Liu, Hong; Shen, Xu; Chen, Kaixian; Jiang, Hualiang

    2004-08-01

    The interaction of a series of indole-2-carboxamide compounds with human liver glycogen phosphorylase a (HLGPa) have been studied employing molecular docking and 3D-QSAR approaches. The Lamarckian Genetic Algorithm (LGA) of AutoDock 3.0 was employed to locate the binding orientations and conformations of the inhibitors interacting with HLGPa. The binding models were demonstrated in the aspects of inhibitor's conformation, subsite interaction, and hydrogen bonding. The very similar binding conformations of these inhibitors show that they interact with HLGPa in a very similar way. Good correlations between the calculated interaction free energies and experimental inhibitory activities suggest that the binding conformations of these inhibitors are reasonable. The structural and energetic differences in inhibitory potencies of indole-2-carboxamide compounds were reasonably explored. Using the binding conformations of indole-2-carboxamides, consistent and highly predictive 3D-QSAR models were developed by CoMFA and CoMSIA analyses. The q2 values are 0.697 and 0.622 for CoMFA and CoMSIA models, respectively. The predictive ability of these models was validated by four compounds that were not included in the training set. Mapping these models back to the topology of the active site of HLGPa leads to a better understanding of the vital indole-2-carboxamide-HLGPa interactions. Structure-based investigations and the final 3D-QSAR results provide clear guidelines and accurate activity predictions for novel inhibitor design.

  8. 3d-transition metal induced enhancement of molecular hydrogen adsorption on Mg(0001) surface: An Ab-initio study

    NASA Astrophysics Data System (ADS)

    Banerjee, Paramita; Das, G. P.

    2016-05-01

    In our effort to do first principles design of suitable materials for hydrogen storage, we have explored the interaction characteristics of a hydrogen molecule with pure as well as a 3d-transition metal (TM) atom doped Mg(0001) surface using density functional theory (DFT) based approach. Doping of a 3d-TM atom by creating a vacancy on the top most layer of Mg(0001) surface, enhances the molecular hydrogen adsorption efficiency of this surface by ~ 6 times. The TM atom gains some charge from the defected site of the Mg(0001) surface, becomes anionic and adsorbs the hydrogen molecule via Anti Kubas-type interaction. The interaction energy of this H2 molecule, including van der Waals dispersion correction, turns out to be ~ 0.4 eV, which falls in the right energy window between physisorption and chemisorption. On full coverage of this 3d-TM atom doped Mg(0001) surface with hydrogen molecules, the gravimetric density of hydrogen has been estimated to be ~ 5.6 wt %, thereby satisfying the criteria set by the department of energy (DOE) for efficient hydrogen storage.

  9. Toward Measuring Galactic Dense Molecular Gas Properties and 3D Distribution with Hi-GAL

    NASA Astrophysics Data System (ADS)

    Zetterlund, Erika; Glenn, Jason; Maloney, Phil

    2016-01-01

    The Herschel Space Observatory's submillimeter dust continuum survey Hi-GAL provides a powerful new dataset for characterizing the structure of the dense interstellar medium of the Milky Way. Hi-GAL observed a 2° wide strip covering the entire 360° of the Galactic plane in broad bands centered at 70, 160, 250, 350, and 500 μm, with angular resolution ranging from 10 to 40 arcseconds. We are adapting a molecular cloud clump-finding algorithm and a distance probability density function distance-determination method developed for the Bolocam Galactic Plane Survey (BGPS) to the Hi-GAL data. Using these methods we expect to generate a database of 105 cloud clumps, derive distance information for roughly half the clumps, and derive precise distances for approximately 20% of them. With five-color photometry and distances, we will measure the cloud clump properties, such as luminosities, physical sizes, and masses, and construct a three-dimensional map of the Milky Way's dense molecular gas distribution.The cloud clump properties and the dense gas distribution will provide critical ground truths for comparison to theoretical models of molecular cloud structure formation and galaxy evolution models that seek to emulate spiral galaxies. For example, such models cannot resolve star formation and use prescriptive recipes, such as converting a fixed fraction of interstellar gas to stars at a specified interstellar medium density threshold. The models should be compared to observed dense molecular gas properties and galactic distributions.As a pilot survey to refine the clump-finding and distance measurement algorithms developed for BGPS, we have identified molecular cloud clumps in six 2° × 2° patches of the Galactic plane, including one in the inner Galaxy along the line of sight through the Molecular Ring and the termination of the Galactic bar and one toward the outer Galaxy. Distances have been derived for the inner Galaxy clumps and compared to Bolocam Galactic Plane

  10. Enterovirus 71 VPg Uridylation Uses a Two-Molecular Mechanism of 3D Polymerase

    PubMed Central

    Sun, Yuna; Wang, Yaxin; Shan, Chao; Chen, Cheng; Xu, Peng; Song, Mohan; Zhou, Honggang; Yang, Cheng; Xu, Wenbo; Shi, Pei-Yong

    2012-01-01

    VPg uridylylation is essential for picornavirus RNA replication. The VPg uridylylation reaction consists of the binding of VPg to 3D polymerase (3Dpol) and the transfer of UMP by 3Dpol to the hydroxyl group of the third amino acid Tyr of VPg. Previous studies suggested that different picornaviruses employ distinct mechanisms during VPg binding and uridylylation. Here, we report a novel site (Site-311, located at the base of the palm domain of EV71 3Dpol) that is essential for EV71 VPg uridylylation as well as viral replication. Ala substitution of amino acids (T313, F314, and I317) at Site-311 reduced the VPg uridylylation activity of 3Dpol by >90%. None of the Site-311 mutations affected the RNA elongation activity of 3Dpol, which indicates that Site-311 does not directly participate in RNA polymerization. However, mutations that abrogated VPg uridylylation significantly reduced the VPg binding ability of 3Dpol, which suggests that Site-311 is a potential VPg binding site on enterovirus 71 (EV71) 3Dpol. Mutation of a polymerase active site in 3Dpol and Site-311 in 3Dpol remarkably enables trans complementation to restore VPg uridylylation. In contrast, two distinct Site-311 mutants do not cause trans complementation in vitro. These results indicate that Site-311 is a VPg binding site that stabilizes the VPg molecule during the VPg uridylylation process and suggest a two-molecule model for 3Dpol during EV71 VPg uridylylation, such that one 3Dpol presents the hydroxyl group of Tyr3 of VPg to the polymerase active site of another 3Dpol, which in turn catalyzes VPg→VPg-pU conversion. For genome-length RNA, the Site-311 mutations that reduced VPg uridylylation were lethal for EV71 replication, which indicates that Site-311 is a potential antiviral target. PMID:23055549

  11. Molecular weight specific impact of soluble and immobilized hyaluronan on CD44 expressing melanoma cells in 3D collagen matrices.

    PubMed

    Sapudom, Jiranuwat; Ullm, Franziska; Martin, Steve; Kalbitzer, Liv; Naab, Johanna; Möller, Stephanie; Schnabelrauch, Matthias; Anderegg, Ulf; Schmidt, Stephan; Pompe, Tilo

    2017-03-01

    Hyaluronan (HA) and its principal receptor CD44 are known to be involved in regulating tumor cell dissemination and metastasis. The direct correlation of CD44-HA interaction on proliferation and invasion of tumor cells in dependence on the molecular weight and the presentation form of HA is not fully understood because of lack of appropriate matrix models. To address this issue, we reconstituted 3D collagen (Coll I) matrices and functionalized them with HA of molecular weight of 30-50kDa (low molecular weight; LMW-HA) and 500-750kDa (high molecular weight; HMW-HA). A post-modification strategy was applied to covalently immobilize HA to reconstituted fibrillar Coll I matrices, resulting in a non-altered Coll I network microstructure and stable immobilization over days. Functionalized Coll I matrices were characterized regarding topological and mechanical characteristics as well as HA amount using confocal laser scanning microscopy, colloidal probe force spectroscopy and quantitative Alcian blue assay, respectively. To elucidate HA dependent tumor cell behavior, BRO melanoma cell lines with and without CD44 receptor expression were used for in vitro cell experiments. We demonstrated that only soluble LMW-HA promoted cell proliferation in a CD44 dependent manner, while HMW-HA and immobilized LMW-HA did not. Furthermore, an enhanced cell invasion was found only for immobilized LMW-HA. Both findings correlated with a very strong and specific adhesive interaction of LMW-HA and CD44+ cells quantified in single cell adhesion measurements using soft colloidal force spectroscopy. Overall, our results introduce an in vitro biomaterials model allowing to test presentation mode and molecular weight specificity of HA in a 3D fibrillar matrix thus mimicking important in vivo features of tumor microenvironments.

  12. Molecular structure studies by 3D imaging of fast ion beams

    SciTech Connect

    Kanter, E.P.; Vager, Z.; Both, G.; Cooney, P.J.; Faibis, A.; Koenig, W.; Zabransky, B.J.; Zajfman, D.

    1986-01-01

    The use of the Coulomb-explosion technique combined with a radically new multi-particle detector, extremely thin film targets, and low-excitation ion source has enabled, for the first time, direct measurements of the complete stereochemistry of complex polyatomic molecular ions. We outline the methods used and present results for protonated acetylene (C/sub 2/H/sub 3//sup +/) and the methane cation (CH/sub 4//sup +/) as examples. We demonstrate the techniques by which these methods can be generalized to determine directly vibrational motions in polyatomic molecules. 24 refs., 4 figs.

  13. Molecular docking and 3D-QSAR studies on gag peptide analogue inhibitors interacting with human cyclophilin A.

    PubMed

    Cui, Meng; Huang, Xiaoqin; Luo, Xiaomin; Briggs, James M; Ji, Ruyun; Chen, Kaixian; Shen, Jianhua; Jiang, Hualiang

    2002-11-21

    The interaction of a series gag peptide analogues with human cyclophilin A (hCypA) have been studied employing molecular docking and 3D-QSAR approaches. The Lamarckian Genetic Algorithm (LGA) and divide-and-conquer methods were applied to locate the binding orientations and conformations of the inhibitors interacting with hCypA. Good correlations between the calculated interaction free energies and experimental inhibitory activities suggest that the binding conformations of these inhibitors are reasonable. A novel interaction model was identified for inhibitors 11, 15, and 17 whose N-termini were modified by addition of the deaminovaline (Dav) group and the C-termini of 15 and 17 were modified by addition of a benzyl group. Accordingly, two new binding sites (sites A and D in Figure 1) were revealed, which show a strong correlation with inhibitor potency and thus can be used as a starting point for new inhibitor design. In addition, two predictive 3D-QSAR models were obtained by CoMFA and CoMSIA analyses based on the binding conformations derived from the molecular docking calculations. The reasonable r(cross)(2) (cross-validated) values 0.738 and 0.762 were obtained for CoMFA and CoMSIA models, respectively. The predictive ability of these models was validated by four peptide analogues test set. The CoMFA and CoMSIA field distributions are in general agreement with the structural characteristics of the binding groove of hCypA. This indicates the reasonableness of the binding model of the inhibitors with hCypA. Considering all these results together with the valuable clues of binding from references published recently, reasonable pharmacophore elements have been suggested, demonstrating that the 3D-QSAR models about peptide analogue inhibitors are expected to be further employed in predicting activities of the novel compounds for inhibiting hCypA.

  14. Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β

    SciTech Connect

    Li, Xiaolin; Ye, Li; Wang, Xiaoxiang; Wang, Xinzhou; Liu, Hongling; Zhu, Yongliang; Yu, Hongxia

    2012-12-15

    Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q{sup 2}) was 0.571 and non-cross-validation correlation coefficient (r{sup 2}) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results. -- Highlights: ► The thyroid hormone activities of HO-PBDEs were studied by 3D-QSAR. ► The binding modes between HO-PBDEs and TRβ were explored. ► 3D-QSAR, molecular docking, and molecular dynamics (MD) methods were performed.

  15. Molecular descriptor data explain market prices of a large commercial chemical compound library

    PubMed Central

    Polanski, Jaroslaw; Kucia, Urszula; Duszkiewicz, Roksana; Kurczyk, Agata; Magdziarz, Tomasz; Gasteiger, Johann

    2016-01-01

    The relationship between the structure and a property of a chemical compound is an essential concept in chemistry guiding, for example, drug design. Actually, however, we need economic considerations to fully understand the fate of drugs on the market. We are performing here for the first time the exploration of quantitative structure-economy relationships (QSER) for a large dataset of a commercial building block library of over 2.2 million chemicals. This investigation provided molecular statistics that shows that on average what we are paying for is the quantity of matter. On the other side, the influence of synthetic availability scores is also revealed. Finally, we are buying substances by looking at the molecular graphs or molecular formulas. Thus, those molecules that have a higher number of atoms look more attractive and are, on average, also more expensive. Our study shows how data binning could be used as an informative method when analyzing big data in chemistry. PMID:27334348

  16. Molecular descriptor data explain market prices of a large commercial chemical compound library.

    PubMed

    Polanski, Jaroslaw; Kucia, Urszula; Duszkiewicz, Roksana; Kurczyk, Agata; Magdziarz, Tomasz; Gasteiger, Johann

    2016-06-23

    The relationship between the structure and a property of a chemical compound is an essential concept in chemistry guiding, for example, drug design. Actually, however, we need economic considerations to fully understand the fate of drugs on the market. We are performing here for the first time the exploration of quantitative structure-economy relationships (QSER) for a large dataset of a commercial building block library of over 2.2 million chemicals. This investigation provided molecular statistics that shows that on average what we are paying for is the quantity of matter. On the other side, the influence of synthetic availability scores is also revealed. Finally, we are buying substances by looking at the molecular graphs or molecular formulas. Thus, those molecules that have a higher number of atoms look more attractive and are, on average, also more expensive. Our study shows how data binning could be used as an informative method when analyzing big data in chemistry.

  17. Molecular descriptor data explain market prices of a large commercial chemical compound library

    NASA Astrophysics Data System (ADS)

    Polanski, Jaroslaw; Kucia, Urszula; Duszkiewicz, Roksana; Kurczyk, Agata; Magdziarz, Tomasz; Gasteiger, Johann

    2016-06-01

    The relationship between the structure and a property of a chemical compound is an essential concept in chemistry guiding, for example, drug design. Actually, however, we need economic considerations to fully understand the fate of drugs on the market. We are performing here for the first time the exploration of quantitative structure-economy relationships (QSER) for a large dataset of a commercial building block library of over 2.2 million chemicals. This investigation provided molecular statistics that shows that on average what we are paying for is the quantity of matter. On the other side, the influence of synthetic availability scores is also revealed. Finally, we are buying substances by looking at the molecular graphs or molecular formulas. Thus, those molecules that have a higher number of atoms look more attractive and are, on average, also more expensive. Our study shows how data binning could be used as an informative method when analyzing big data in chemistry.

  18. Binary classification of chalcone derivatives with LDA or KNN based on their antileishmanial activity and molecular descriptors selected using the Successive Projections Algorithm feature-selection technique.

    PubMed

    Goodarzi, Mohammad; Saeys, Wouter; de Araujo, Mario Cesar Ugulino; Galvão, Roberto Kawakami Harrop; Vander Heyden, Yvan

    2014-01-23

    Chalcones are naturally occurring aromatic ketones, which consist of an α-, β-unsaturated carbonyl system joining two aryl rings. These compounds are reported to exhibit several pharmacological activities, including antiparasitic, antibacterial, antifungal, anticancer, immunomodulatory, nitric oxide inhibition and anti-inflammatory effects. In the present work, a Quantitative Structure-Activity Relationship (QSAR) study is carried out to classify chalcone derivatives with respect to their antileishmanial activity (active/inactive) on the basis of molecular descriptors. For this purpose, two techniques to select descriptors are employed, the Successive Projections Algorithm (SPA) and the Genetic Algorithm (GA). The selected descriptors are initially employed to build Linear Discriminant Analysis (LDA) models. An additional investigation is then carried out to determine whether the results can be improved by using a non-parametric classification technique (One Nearest Neighbour, 1NN). In a case study involving 100 chalcone derivatives, the 1NN models were found to provide better rates of correct classification than LDA, both in the training and test sets. The best result was achieved by a SPA-1NN model with six molecular descriptors, which provided correct classification rates of 97% and 84% for the training and test sets, respectively.

  19. Optoacoustic system for 3D functional and molecular imaging in nude mice

    NASA Astrophysics Data System (ADS)

    Fronheiser, Matthew P.; Stein, Alan; Herzog, Don; Thompson, Scott; Liopo, Anton; Eghtedari, Mohammad; Motamedi, Massoud; Ermilov, Sergey; Conjusteau, Andre; Gharieb, Reda; Lacewell, Ron; Miller, Tom; Mehta, Ketan; Oraevsky, Alexander A.

    2008-02-01

    A three-dimensional laser optoacoustic imaging system was developed, which combines the advantages of optical spectroscopy and high resolution ultrasonic detection, to produce high contrast maps of optical absorbance in tissues. This system was tested in a nude mouse model of breast cancer and produced tissue images of tumors and vasculature. The imaging can utilize either optical properties of hemoglobin and oxyhemoglobin, which are the main endogenous tissue chromophores in the red and near-infrared spectral ranges, or exogenous contrast agent based on gold nanorods. Visualization of tissue molecules targeted by the contrast agent provides molecular information. Visulization of blood at multiple colors of light provides functional information on blood concentration and oxygen saturation. Optoacoustic imaging, using two or more laser illumination wavelengths, permits an assessment of the angiogenesis-related microvasculature, and thereby, an evaluation of the tumor stage and its metastatic potential. The optoacoustic imaging system was also used to generate molecular images of the malignancy-related receptors induced by the xenografts of BT474 mammary adenocarcinoma cells in nude mice. The development of the latter images was facilitated by the use of an optoacoustic contrast agent that utilizes gold nanorods conjugated to monoclonal antibody raised against HER2/neu antigens. These nanorods possess a very strong optical absorption peak that can be tuned in the near-infrared by changing their aspect ratio. The effective conversion of the optical energy into heat by the gold nanorods, followed by the thermal expansion of the surrounding water, makes these nanoparticles an effective optoacoustic contrast agent. Optical scattering methods and x-ray tomography may also benefit from the application of this contrast agent. Administration of the gold nanorod bioconjugates to mice resulted in an enhanced contrast of breast tumors relative the background of normal tissues

  20. Chemometric Methods and Theoretical Molecular Descriptors in Predictive QSAR Modeling of the Environmental Behavior of Organic Pollutants

    NASA Astrophysics Data System (ADS)

    Gramatica, Paola

    This chapter surveys the QSAR modeling approaches (developed by the author's research group) for the validated prediction of environmental properties of organic pollutants. Various chemometric methods, based on different theoretical molecular descriptors, have been applied: explorative techniques (such as PCA for ranking, SOM for similarity analysis), modeling approaches by multiple-linear regression (MLR, in particular OLS), and classification methods (mainly k-NN, CART, CP-ANN). The focus of this review is on the main topics of environmental chemistry and ecotoxicology, related to the physico-chemical properties, the reactivity, and biological activity of chemicals of high environmental concern. Thus, the review deals with atmospheric degradation reactions of VOCs by tropospheric oxidants, persistence and long-range transport of POPs, sorption behavior of pesticides (Koc and leaching), bioconcentration, toxicity (acute aquatic toxicity, mutagenicity of PAHs, estrogen binding activity for endocrine disruptors compounds (EDCs)), and finally persistent bioaccumulative and toxic (PBT) behavior for the screening and prioritization of organic pollutants. Common to all the proposed models is the attention paid to model validation for predictive ability (not only internal, but also external for chemicals not participating in the model development) and checking of the chemical domain of applicability. Adherence to such a policy, requested also by the OECD principles, ensures the production of reliable predicted data, useful also in the new European regulation of chemicals, REACH.

  1. Partition Coefficients of Organics between Water and Carbon Dioxide Revisited: Correlation with Solute Molecular Descriptors and Solvent Cohesive Properties.

    PubMed

    Roth, Michal

    2016-12-06

    High-pressure phase behavior of systems containing water, carbon dioxide and organics has been important in several environment- and energy-related fields including carbon capture and storage, CO2 sequestration and CO2-assisted enhanced oil recovery. Here, partition coefficients (K-factors) of organic solutes between water and supercritical carbon dioxide have been correlated with extended linear solvation energy relationships (LSERs). In addition to the Abraham molecular descriptors of the solutes, the explanatory variables also include the logarithm of solute vapor pressure, the solubility parameters of carbon dioxide and water, and the internal pressure of water. This is the first attempt to include also the properties of water as explanatory variables in LSER correlations of K-factor data in CO2-water-organic systems. Increasing values of the solute hydrogen bond acidity, the solute hydrogen bond basicity, the solute dipolarity/polarizability, the internal pressure of water and the solubility parameter of water all tend to reduce the K-factor, that is, to favor the solute partitioning to the water-rich phase. On the contrary, increasing values of the solute characteristic volume, the solute vapor pressure and the solubility parameter of CO2 tend to raise the K-factor, that is, to favor the solute partitioning to the CO2-rich phase.

  2. Combination of molecular dynamics method and 3D-RISM theory for conformational sampling of large flexible molecules in solution.

    PubMed

    Miyata, Tatsuhiko; Hirata, Fumio

    2008-04-30

    We have developed an algorithm for sampling the conformational space of large flexible molecules in solution, which combines the molecular dynamics (MD) method and the three-dimensional reference interaction site model (3D-RISM) theory. The solvent-induced force acting on solute atoms was evaluated as the gradient of the solvation free energy with respect to the solute-atom coordinates. To enhance the computation speed, we have applied a multiple timestep algorithm based on the RESPA (Reversible System Propagator Algorithm) to the combined MD/3D-RISM method. By virtue of the algorithm, one can choose a longer timestep for renewing the solvent-induced force compared with that of the conformational update. To illustrate the present MD/3D-RISM simulation, we applied the method to a model of acetylacetone in aqueous solution. The multiple timestep algorithm succeeded in enhancing the computation speed by 3.4 times for this model case. Acetylacetone possesses an intramolecular hydrogen-bonding capability between the hydroxyl group and the carbonyl oxygen atom, and the molecule is significantly stabilized due to this hydrogen bond, especially in gas phase. The intramolecular hydrogen bond was kept intact during almost entire course of the MD simulation in gas phase, while in the aqueous solutions the bond is disrupted in a significant number of conformations. This result qualitatively agrees with the behavior on a free energy barrier lying upon the process for rotating a torsional degree of freedom of the hydroxyl group, where it is significantly reduced in aqueous solution by a cancellation between the electrostatic interaction and the solvation free energy.

  3. Mammalian olfactory receptors: molecular mechanisms of odorant detection, 3D-modeling, and structure-activity relationships.

    PubMed

    Persuy, Marie-Annick; Sanz, Guenhaël; Tromelin, Anne; Thomas-Danguin, Thierry; Gibrat, Jean-François; Pajot-Augy, Edith

    2015-01-01

    This chapter describes the main characteristics of olfactory receptor (OR) genes of vertebrates, including generation of this large multigenic family and pseudogenization. OR genes are compared in relation to evolution and among species. OR gene structure and selection of a given gene for expression in an olfactory sensory neuron (OSN) are tackled. The specificities of OR proteins, their expression, and their function are presented. The expression of OR proteins in locations other than the nasal cavity is regulated by different mechanisms, and ORs display various additional functions. A conventional olfactory signal transduction cascade is observed in OSNs, but individual ORs can also mediate different signaling pathways, through the involvement of other molecular partners and depending on the odorant ligand encountered. ORs are engaged in constitutive dimers. Ligand binding induces conformational changes in the ORs that regulate their level of activity depending on odorant dose. When present, odorant binding proteins induce an allosteric modulation of OR activity. Since no 3D structure of an OR has been yet resolved, modeling has to be performed using the closest G-protein-coupled receptor 3D structures available, to facilitate virtual ligand screening using the models. The study of odorant binding modes and affinities may infer best-bet OR ligands, to be subsequently checked experimentally. The relationship between spatial and steric features of odorants and their activity in terms of perceived odor quality are also fields of research that development of computing tools may enhance.

  4. Molecular docking and 3D-QSAR studies on the glucocorticoid receptor antagonistic activity of hydroxylated polychlorinated biphenyls.

    PubMed

    Liu, S; Luo, Y; Fu, J; Zhou, J; Kyzas, G Z

    2016-01-01

    The glucocorticoid receptor (GR) antagonistic activities of hydroxylated polychlorinated biphenyls (HO-PCBs) were recently characterised. To further explore the interactions between HO-PCBs and the GR, and to elucidate structural characteristics that influence the GR antagonistic activity of HO-PCBs, molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed. Comparative molecular similarity indices analysis (CoMSIA) was performed using both ligand- and receptor-based alignment schemes. Results generated from the receptor-based model were found to be more satisfactory, with q(2) of 0.632 and r(2) of 0.931 compared with those from the ligand-based model. Some internal validation strategies (e.g. cross-validation analysis, bootstrapping analysis and Y-randomisation) and an external validation method were used respectively to further assess the stability and predictive ability of the derived model. Graphical interpretation of the model provided some insights into the structural features that affected the GR antagonistic activity of HO-PCBs. Molecular docking studies revealed that some key residues were critical for ligand-receptor interactions by forming hydrogen bonds (Glu540) and hydrophobic interactions with ligands (Ile539, Val543 and Trp577). Although CoMSIA sometimes depends on the alignment of the molecules, the information provided is beneficial for predicting the GR antagonistic activities of HO-PCB homologues and is helpful for understanding the binding mechanisms of HO-PCBs to GR.

  5. Exploration of Novel Inhibitors for Bruton’s Tyrosine Kinase by 3D QSAR Modeling and Molecular Dynamics Simulation

    PubMed Central

    Choi, Light; Woo Lee, Keun

    2016-01-01

    Bruton’s tyrosine kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase which is expressed in most of the hematopoietic cells and plays an important role in many cellular signaling pathways. B cell malignancies are dependent on BCR signaling, thus making BTK an efficient therapeutic target. Over the last few years, significant efforts have been made in order to develop BTK inhibitors to treat B-cell malignancies, and autoimmunity or allergy/hypersensitivity but limited success has been achieved. Here in this study, 3D QSAR pharmacophore models were generated for Btk based on known IC50 values and experimental energy scores with extensive validations. The five features pharmacophore model, Hypo1, includes one hydrogen bond acceptor lipid, one hydrogen bond donor, and three hydrophobic features, which has the highest correlation coefficient (0.98), cost difference (112.87), and low RMS (1.68). It was further validated by the Fisher’s randomization method and test set. The well validated Hypo1 was used as a 3D query to search novel Btk inhibitors with different chemical scaffold using high throughput virtual screening technique. The screened compounds were further sorted by applying ADMET properties, Lipinski’s rule of five and molecular docking studies to refine the retrieved hits. Furthermore, molecular dynamic simulation was employed to study the stability of docked conformation and to investigate the binding interactions in detail. Several important hydrogen bonds with Btk were revealed, which includes the gatekeeper residues Glu475 and Met 477 at the hinge region. Overall, this study suggests that the proposed hits may be more effective inhibitors for cancer and autoimmune therapy. PMID:26784025

  6. Molecular docking and 3D-quantitative structure activity relationship analyses of peptidyl vinyl sulfones: Plasmodium Falciparum cysteine proteases inhibitors

    NASA Astrophysics Data System (ADS)

    Teixeira, Cátia; Gomes, José R. B.; Couesnon, Thierry; Gomes, Paula

    2011-08-01

    Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were conducted on a series (39 molecules) of peptidyl vinyl sulfone derivatives as potential Plasmodium Falciparum cysteine proteases inhibitors. Two different methods of alignment were employed: (i) a receptor-docked alignment derived from the structure-based docking algorithm GOLD and (ii) a ligand-based alignment using the structure of one of the ligands derived from a crystal structure from the PDB databank. The best predictions were obtained for the receptor-docked alignment with a CoMFA standard model ( q 2 = 0.696 and r 2 = 0.980) and with CoMSIA combined electrostatic, and hydrophobic fields ( q 2 = 0.711 and r 2 = 0.992). Both models were validated by a test set of nine compounds and gave satisfactory predictive r 2 pred values of 0.76 and 0.74, respectively. CoMFA and CoMSIA contour maps were used to identify critical regions where any change in the steric, electrostatic, and hydrophobic fields may affect the inhibitory activity, and to highlight the key structural features required for biological activity. Moreover, the results obtained from 3D-QSAR analyses were superimposed on the Plasmodium Falciparum cysteine proteases active site and the main interactions were studied. The present work provides extremely useful guidelines for future structural modifications of this class of compounds towards the development of superior antimalarials.

  7. 3D-chiral Atom, Atom-type, and Total Non-stochastic and Stochastic Molecular Linear Indices and their Applications to Central Chirality Codification

    NASA Astrophysics Data System (ADS)

    Marrero-Ponce, Yovani; Castillo-Garit, Juan A.

    2005-06-01

    Non-stochastic and stochastic 2D linear indices have been generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D-chirality correction factor. These descriptors circumvent the inability of conventional 2D non-stochastic [Y. Marrero-Ponce. J. Chem. Inf. Comp., Sci. l 44 (2004) 2010] and stochastic [Y. Marrero-Ponce, et al. Bioorg. Med. Chem., 13 (2005) 1293] linear indices to distinguish σ-stereoisomers. In order to test the potential of this novel approach in drug design we have modelled the angiotensin-converting enzyme inhibitory activity of perindoprilate's σ-stereoisomers combinatorial library. Two linear discriminant analysis models, using non-stochastic and stochastic linear indices, were obtained. The models showed an accuracy of 100% and 96.65% for the training set; and 88.88% and 100% in the external test set, respectively. Canonical regression analysis corroborated the statistical quality of these models ( R can of 0.78 and of 0.77) and was also used to compute biology activity canonical scores for each compound. After that, the prediction of the σ-receptor antagonists of chiral 3-(3-hydroxyphenyl)piperidines by linear multiple regression analysis was carried out. Two statistically significant QSAR models were obtained when non-stochastic ( R 2 = 0.982 and s = 0.157) and stochastic ( R 2 = 0.941 and s = 0.267) 3D-chiral linear indices were used. The predictive power was assessed by the leave-one-out cross-validation experiment, yielding values of q 2 = 0.982 ( s cv = 0.186) and q 2 = 0.90 ( s cv = 0.319), respectively. Finally, the prediction of the corticosteroid-binding globulin binding affinity of steroids set was performed. The best results obtained in the cross-validation procedure with non-stochastic ( q 2 = 0.904) and stochastic ( q 2 = 0.88) 3D-chiral linear indices are rather similar to most of the 3D-QSAR approaches reported so far. The validation of this method was achieved by comparison with

  8. Relationship between reaction rate constants of organic pollutants and their molecular descriptors during Fenton oxidation and in situ formed ferric-oxyhydroxides.

    PubMed

    Jia, Lijuan; Shen, Zhemin; Su, Pingru

    2016-05-01

    Fenton oxidation is a promising water treatment method to degrade organic pollutants. In this study, 30 different organic compounds were selected and their reaction rate constants (k) were determined for the Fenton oxidation process. Gaussian09 and Material Studio software sets were used to carry out calculations and obtain values of 10 different molecular descriptors for each studied compound. Ferric-oxyhydroxide coagulation experiments were conducted to determine the coagulation percentage. Based upon the adsorption capacity, all of the investigated organic compounds were divided into two groups (Group A and Group B). The percentage adsorption of organic compounds in Group A was less than 15% (wt./wt.) and that in the Group B was higher than 15% (wt./wt.). For Group A, removal of the compounds by oxidation was the dominant process while for Group B, removal by both oxidation and coagulation (as a synergistic process) took place. Results showed that the relationship between the rate constants (k values) and the molecular descriptors of Group A was more pronounced than for Group B compounds. For the oxidation-dominated process, EHOMO and Fukui indices (f(0)x, f(-)x, f(+)x) were the most significant factors. The influence of bond order was more significant for the synergistic process of oxidation and coagulation than for the oxidation-dominated process. The influences of all other molecular descriptors on the synergistic process were weaker than on the oxidation-dominated process.

  9. Free radical reactions of isoxazole and pyrazole derivatives of hispolon: kinetics correlated with molecular descriptors.

    PubMed

    Shaikh, Shaukat Ali M; Barik, Atanu; Singh, Beena G; Modukuri, Ramani V; Balaji, Neduri V; Subbaraju, Gottumukkala V; Naik, Devidas B; Priyadarsini, K Indira

    2016-12-01

    Hispolon (HS), a natural polyphenol found in medicinal mushrooms, and its isoxazole (HI) and pyrazole (HP) derivatives have been examined for free radical reactions and in vitro antioxidant activity. Reaction of these compounds with one-electron oxidant, azide radicals ([Formula: see text]) and trichloromethyl peroxyl radicals ([Formula: see text]), model peroxyl radicals, studied by nanosecond pulse radiolysis technique, indicated formation of phenoxyl radicals absorbing at 420 nm with half life of few hundred microseconds (μs). The formation of phenoxyl radicals confirmed that the phenolic OH is the active centre for free radical reactions. Rate constant for the reaction of these radicals with these compounds were in the order kHI ≅ kHP > kHS. Further the compounds were examined for their ability to inhibit lipid peroxidation in model membranes and also for the scavenging of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical and superoxide ([Formula: see text]) radicals. The results suggested that HP and HI are less efficient than HS towards these radical reactions. Quantum chemical calculations were performed on these compounds to understand the mechanism of reaction with different radicals. Lower values of adiabatic ionization potential (AIP) and elevated highest occupied molecular orbital (HOMO) for HI and HP compared with HS controlled their activity towards [Formula: see text] and [Formula: see text] radicals, whereas the contribution of overall anion concentration was responsible for higher activity of HS for DPPH, [Formula: see text], and lipid peroxyl radical. The results confirm the role of different structural moieties on the antioxidant activity of hispolon derivatives.

  10. Molecular tectonics: self-complementary supramolecular Se...N synthons directing assembly of 1D silver chains into 3D porous molecular architectures.

    PubMed

    Zhou, Ai-Ju; Zheng, Shao-Liang; Fang, Yue; Tong, Ming-Liang

    2005-06-27

    Reaction of 2,1,3-benzoselenadiazole (bsd) with AgNO3 results in the formation of a novel model example of a Se...N synthon directed molecular network of different polymorphs at different temperatures. Alpha-[Ag(bsd)2(NO3)] x 0.5bsd formed at ambient temperature, has a 3D porous molecular network constructed with monomeric [Ag(bsd)2(NO3)] motif, and has 1D channels that are encapsulated with 1D arrays of two-fold-disordered dimeric (bsd)2 guests aggregated by the self-complementary nonbonded Se...N interactions. This is the first molecular net directed by supramolecular Se...N synthons. The second polymorph, beta-[Ag(bsd)2(NO3)] x 0.5bsd, formed from an analogous reaction at 50 degrees C, contains a similar 3D molecular network constructed with tetrameric [Ag4(bsd)8(NO3)4] motif and 1D arrays of well-ordered dimeric (bsd)2 guests are encapsulated in the channels. Such ordered (bsd)2 dimers provide an excellent simplified dimeric model for MO calculations of intermolecular nonbonded Se...N interactions.

  11. 3D-QSAR and molecular docking studies of selective agonists for the thyroid hormone receptor beta.

    PubMed

    Du, Juan; Qin, Jin; Liu, Huanxiang; Yao, Xiaojun

    2008-09-01

    Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed using comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) on a series of agonists of thyroid hormone receptor beta (TRbeta), which may lead to safe therapies for non-thyroid disorders while avoiding the cardiac side effects. The reasonable q(2) (cross-validated) values 0.600 and 0.616 and non-cross-validated r(2) values of 0.974 and 0.974 were obtained for CoMFA and CoMSIA models for the training set compounds, respectively. The predictive ability of two models was validated using a test set of 12 molecules which gave predictive correlation coefficients (r(pred)(2)) of 0.688 and 0.674, respectively. The Lamarckian Genetic Algorithm (LGA) of AutoDock 4.0 was employed to explore the binding mode of the compound at the active site of TRbeta. The results not only lead to a better understanding of interactions between these agonists and the thyroid hormone receptor beta but also can provide us some useful information about the influence of structures on the activity which will be very useful for designing some new agonist with desired activity.

  12. The case for intrinsically disordered proteins playing contributory roles in molecular recognition without a stable 3D structure

    PubMed Central

    Uversky, Vladimir N.

    2013-01-01

    The classical ‘lock-and-key’ and ‘induced-fit’ mechanisms for binding both originated in attempts to explain features of enzyme catalysis. For both of these mechanisms and for their recent refinements, enzyme catalysis requires exquisite spatial and electronic complementarity between the substrate and the catalyst. Thus, binding models derived from models originally based on catalysis will be highly biased towards mechanisms that utilize structural complementarity. If mere binding without catalysis is the endpoint, then the structural requirements for the interaction become much more relaxed. Recent observations on specific examples suggest that this relaxation can reach an extreme lack of specific 3D structure, leading to molecular recognition with biological consequences that depend not only upon structural and electrostatic complementarity between the binding partners but also upon kinetic, entropic, and generalized electrostatic effects. In addition to this discussion of binding without fixed structure, examples in which unstructured regions carry out important biological functions not involving molecular recognition will also be discussed. Finally, we discuss whether ‘intrinsically disordered protein’ (IDP) represents a useful new concept. PMID:23361308

  13. In vitro modeling of angiotensin-converting enzyme inhibitor's absorption with chromatographic retention data and selected molecular descriptors.

    PubMed

    Odović, Jadranka; Marković, Bojan; Vladimirov, Sote; Karljiković-Rajić, Katarina

    2014-03-15

    Set of nine angiotensin-converting enzyme inhibitors (enalapril, quinapril, fosinopril, lisinopril, cilazapril, ramipril, benazepril, perindopril and moexipril) were studied to evaluate the correlation between their intestinal absorption and salting-out thin-layer chromatography hydrophobicity parameters (RM(0) or C0) obtained by ascending technique applying four different salts, (NH4)2SO4, NH4NO3, NH4Cl and NaCl as mobile phases. The best correlations between KOWWIN logP and both hydrophobicity parameters, RM(0) and C0, (R(2)>0.850) were observed for NaCl (1.0-3.0M) while the lowest R(2) was obtained for (NH4)2SO4 (0.649 and 0.427, respectively) due to highest salting-out effect of (NH4)2SO4. The effect of selected inorganic salts in the salting-out mobile phases, on the solutes solubility and retention was evaluated. The topological polar surface area should be selected as independent variable (only this molecular descriptor showed low correlation with chromatographic hydrophobicity parameters) for multiple linear regression analysis, to obtain reliable correlation between angiotensin-converting enzyme inhibitor's intestinal absorption data and salting-out thin-layer chromatograpic hydrophobicity parameters. These correlations provide R(2)=0.823 for RM(0) or R(2)=0.799 for C0 indicating good relationship between predicted and literature available intestinal absorption (ranged from 22% to 70%) of investigated angiotensin-converting enzyme inhibitors. The proposed in vitro model was checked with three in addition experimentally analyzed drugs, zofenopril, trandolapril and captoril. The satisfactory absorption prediction was obtained for zofenopril and trandolapril, while divergence established for captopril resulted from considerably different structure.

  14. Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions.

    PubMed

    Fletcher, John S; Lockyer, Nicholas P; Vickerman, John C

    2011-01-01

    In principle mass spectral imaging has enormous potential for discovery applications in biology. The chemical specificity of mass spectrometry combined with spatial analysis capabilities of liquid metal cluster beams and the high yields of polyatomic ion beams should present unprecedented ability to spatially locate molecular chemistry in the 100 nm range. However, although metal cluster ion beams have greatly increased yields in the m/z range up to 1000, they still have to be operated under the static limit and even in most favorable cases maximum yields for molecular species from 1 µm pixels are frequently below 20 counts. However, some very impressive molecular imaging analysis has been accomplished under these conditions. Nevertheless although molecular ions of lipids have been detected and correlation with biology is obtained, signal levels are such that lateral resolution must be sacrificed to provide a sufficient signal to image. To obtain useful spatial resolution detection below 1 µm is almost impossible. Too few ions are generated! The review shows that the application of polyatomic primary ions with their low damage cross-sections offers hope of a new approach to molecular SIMS imaging by accessing voxels rather than pixels to thereby increase the dynamic signal range in 2D imaging and to extend the analysis to depth profiling and 3D imaging. Recent data on cells and tissue analysis suggest that there is, in consequence, the prospect that a wider chemistry might be accessible within a sub-micron area and as a function of depth. However, these advances are compromised by the pulsed nature of current ToF-SIMS instruments. The duty cycle is very low and results in excessive analysis times, and maximum mass resolution is incompatible with maximum spatial resolution. New instrumental directions are described that enable a dc primary beam to be used that promises to be able to take full advantage of all the capabilities of the polyatomic ion beam. Some new

  15. Calculation of Local Water Densities in Biological Systems — A Comparison of Molecular Dynamics Simulations and the 3D-RISM-KH Molecular Theory of Solvation

    PubMed Central

    Stumpe, Martin C.; Blinov, Nikolay; Wishart, David; Kovalenko, Andriy; Pande, Vijay S.

    2010-01-01

    Water plays a unique role in all living organisms. Not only is it nature’s ubiquitous solvent, but it also actively takes part in many cellular processes. In particular, the structure and properties of interfacial water near biomolecules like proteins are often related to the function of the respective molecule. It can therefore be highly instructive to study the local water density around solutes in cellular systems, particularly when solvent-mediated forces like the hydrophobic effect are relevant. Computational methods like molecular dynamics (MD) simulations seem well suited to study these systems at the atomic level. However, due to sampling requirements, it is not clear that MD simulations are indeed the method of choice to obtain converged densities at a given level of precision. We here compare the calculation of local water densities with two different methods, MD simulations and the three-dimensional reference interaction site model with the Kovalenko-Hirata closure (3D-RISM-KH). In particular, we investigate the convergence of the local water density to assess the required simulation times for different levels of resolution. Moreover, we provide a quantitative comparison of the densities calculated with MD and with 3D-RISM-KH, and investigate the effect of the choice of the water model for both methods. Our results show that 3D-RISM-KH yields density distributions that are very similar to those from MD up to a 0.5 Å resolution, but for significantly reduced computational cost. The combined use of MD and 3D-RISM-KH emerges as an auspicious perspective for efficient solvent sampling in dynamical systems. PMID:21174421

  16. Synthesis of novel anthraquinones: Molecular structure, molecular chemical reactivity descriptors and interactions with DNA as antibiotic and anti-cancer drugs

    NASA Astrophysics Data System (ADS)

    Al-Otaibi, Jamelah S.; EL Gogary, Tarek M.

    2017-02-01

    Anthraquinones are well-known anticancer drugs. Anthraquinones anticancer drugs carry out their cytotoxic activities through their interaction with DNA, and inhibition of topoisomerase II activity. Anthraquinones (AQ5 and AQ5H) were synthesized and studied with 1,5-DAAQ by computational and experimental tools. The purpose of this study is to shade more light on mechanism of interaction between anthraquinone DNA affinic agents and different types of DNA. This study will lead to gain of information useful for drug design and development. Molecular structures were optimized using DFT B3LYP/6-31 + G(d). Depending on intramolecular hydrogen bonding interactions four conformers of AQ5 were detected within the range of about 42 kcal/mol. Molecular reactivity of the anthraquinone compounds was explored using global and condensed descriptors (electrophilicity and Fukui functions). NMR and UV-VIS electronic absorption spectra of anthraquinones/DNA were investigated at the physiological pH. The interaction of the anthraquinones (AQ5 and AQ5H) were studied with different DNA namely, calf thymus DNA, (Poly[dA].Poly[dT]) and (Poly[dG].Poly[dC]). UV-VIS electronic absorption spectral data were employed to measure the affinity constants of drug/DNA binding using Scatchard analysis. NMR study confirms qualitatively the drug/DNA interaction in terms of peak shift and broadening.

  17. 3D Structure Generation, Molecular Dynamics and Docking Studies of IRHOM2 Protein Involved in Cancer & Rheumatoid Arthritis.

    PubMed

    Raj, Utkarsh; Kumar, Himansu; Varadwaj, Pritish Kumar

    2015-01-01

    A short-lived membrane protein IRHOM2 pedals a cascade of events by regulating Epidermal Growth Factor Receptor (EGFR) signalling in parallel with metalloproteases which results their involvement in cancer as well as in rheumatoid arthritis. Therefore, IRHOM2 is a potential therapeutic drug target for these diseases, but its 3D-structure has not been reported yet. In this study, the three-dimensional structure of the IRHOM2 protein was generated using I-TASSER (Iterative Threading Assembly Refinement) server. The modeled structure of IRHOM2 receptor was validated using various Structural Analysis and Verification Server (SAVES) in which 99.7% of amino acid residues are present in the favoured regions of the Ramachandran Plot. Further, the refined modeled structure was subjected to molecular dynamics simulation & docking analysis. Virtual screening studies were carried out using Glide with various selective libraries containing 24552 compounds and the analysis indicated extensive hydrogen bonding network and hydrophobic interactions which play a significant role in its binding. Docking results were analyzed for high ranking compounds using a consensus based docking score to calculate the binding affinity as a measure of protein-ligand interactions. The top ranking molecule against IRHOM2 active site has a glide g-score of -12.565 kcal/mol and glide e-model score of -74.967 with 3 hydrogen bonds and 11 hydrophobic contacts. This compound may act as probable inhibitor against these chronic diseases but further in vitro studies are required.

  18. An in-depth spectroscopic examination of molecular bands from 3D hydrodynamical model atmospheres. I. Formation of the G-band in metal-poor dwarf stars

    NASA Astrophysics Data System (ADS)

    Gallagher, A. J.; Caffau, E.; Bonifacio, P.; Ludwig, H.-G.; Steffen, M.; Spite, M.

    2016-09-01

    Context. Recent developments in the three-dimensional (3D) spectral synthesis code Linfor3D have meant that for the first time, large spectral wavelength regions, such as molecular bands, can be synthesised with it in a short amount of time. Aims: A detailed spectral analysis of the synthetic G-band for several dwarf turn-off-type 3D atmospheres (5850 ≲ Teff [ K ] ≲ 6550, 4.0 ≤ log g ≤ 4.5, - 3.0 ≤ [Fe/H] ≤-1.0) was conducted, under the assumption of local thermodynamic equilibrium. We also examine carbon and oxygen molecule formation at various metallicity regimes and discuss the impact it has on the G-band. Methods: Using a qualitative approach, we describe the different behaviours between the 3D atmospheres and the traditional one-dimensional (1D) atmospheres and how the different physics involved inevitably leads to abundance corrections, which differ over varying metallicities. Spectra computed in 1D were fit to every 3D spectrum to determine the 3D abundance correction. Results: Early analysis revealed that the CH molecules that make up the G-band exhibited an oxygen abundance dependency; a higher oxygen abundance leads to weaker CH features. Nitrogen abundances showed zero impact to CH formation. The 3D corrections are also stronger at lower metallicity. Analysis of the 3D corrections to the G-band allows us to assign estimations of the 3D abundance correction to most dwarf stars presented in the literature. Conclusions: The 3D corrections suggest that A(C) in carbon-enhanced metal-poor (CEMP) stars with high A(C) would remain unchanged, but would decrease in CEMP stars with lower A(C). It was found that the C/O ratio is an important parameter to the G-band in 3D. Additional testing confirmed that the C/O ratio is an equally important parameter for OH transitions under 3D. This presents a clear interrelation between the carbon and oxygen abundances in 3D atmospheres through their molecular species, which is not seen in 1D.

  19. Relationships Between MRI Breast Imaging-Reporting and Data System (BI-RADS) Lexicon Descriptors and Breast Cancer Molecular Subtypes: Internal Enhancement is Associated with Luminal B Subtype.

    PubMed

    Grimm, Lars J; Zhang, Jing; Baker, Jay A; Soo, Mary S; Johnson, Karen S; Mazurowski, Maciej A

    2017-03-13

    The aim of this study was to determine the associations between breast MRI findings using the Breast Imaging-Reporting and Data System (BI-RADS) lexicon descriptors and breast cancer molecular subtypes. In this retrospective, IRB-approved, single institution study MRIs from 278 women with breast cancer were reviewed by one of six fellowship-trained breast imagers. Readers reported BI-RADS descriptors for breast masses (shape, margin, internal enhancement) and non-mass enhancement (distribution, internal enhancement). Pathology reports were reviewed for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Surrogates were used to categorize tumors by molecular subtype: ER/PR+, HER2- (luminal A); ER/PR+, HER2+ (luminal B); ER/PR-, HER2+ (HER2); ER/PR/HER2- (basal). A univariate logistic regression model was developed to identify associations between BI-RADS descriptors and molecular subtypes. Internal enhancement for mass and non-mass enhancement was combined for analysis. There was an association between mass shape and basal subtype (p = 0.039), which was more frequently round (17.1%) than other subtypes (range: 0-8.3%). In addition, there was an association between mass margin and HER2 subtype (p = 0.040), as HER2 cancers more frequently had a smooth margin (33.3%) than other subtypes (range: 4.2-17.1%). Finally, there was an association between internal enhancement and luminal B subtype (p = 0.003), with no cases of luminal B cancer demonstrating homogeneous internal enhancement versus a range of 10.9-23.5% for other subtypes. There are associations between breast cancer molecular subtypes and lesion appearance on MRI using the BI-RADS lexicon.

  20. A combination of pharmacophore modeling, atom-based 3D-QSAR, molecular docking and molecular dynamics simulation studies on PDE4 enzyme inhibitors.

    PubMed

    Tripuraneni, Naga Srinivas; Azam, Mohammed Afzal

    2016-11-01

    Phosphodiesterases 4 enzyme is an attractive target for the design of anti-inflammatory and bronchodilator agents. In the present study, pharmacophore and atom-based 3D-QSAR studies were carried out for pyrazolopyridine and quinoline derivatives using Schrödinger suite 2014-3. A four-point pharmacophore model was developed using 74 molecules having pIC50 ranging from 10.1 to 4.5. The best four feature model consists of one hydrogen bond acceptor, two aromatic rings, and one hydrophobic group. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a high correlation coefficient (R(2 )= .9949), cross validation coefficient (Q(2 )= .7291), and Pearson-r (.9107) at six component partial least square factor. The external validation indicated that our QSAR model possessed high predictive power with R(2) value of .88. The generated model was further validated by enrichment studies using the decoy test. Molecular docking, free energy calculation, and molecular dynamics (MD) simulation studies have been performed to explore the putative binding modes of these ligands. A 10-ns MD simulation confirmed the docking results of both stability of the 1XMU-ligand complex and the presumed active conformation. Outcomes of the present study provide insight in designing novel molecules with better PDE4 inhibitory activity.

  1. Hot molecular hydrogen in the central parsec of the Galaxy through near-infrared 3D fitting

    NASA Astrophysics Data System (ADS)

    Ciurlo, A.; Paumard, T.; Rouan, D.; Clénet, Y.

    2016-10-01

    Aims: We have investigated neutral gas in the central cavity of the circumnuclear disk (CND) at the Galactic center, where the ionized minispiral lies, to describe the H2 distribution and properties in this ionized environment. Methods: This study was carried out through a spectro-imaging data cube of the central cavity obtained with SPIFFI on the VLT. The observed field of view is 36″ × 29″, with a spectral resolution R = 1300 in the near-infrared. These observations cover several H2 lines. To preserve the spatial resolution and avoid edge effects, we applied a new line-fitting method that consists of a regularized 3D fitting. We also applied a more classical 1D fitting to compare the relative strength of the H2 lines. Results: We present high spatial and spectral resolution maps of the intensity, velocity, and width of five H2 lines and an extinction map derived from H2. Molecular gas is detected everywhere in the field. In particular, in addition to the known CND features, we detected an emission from the northern arm cloud and from the minicavity. The excitation diagrams allow us to estimate the temperature, mass, and density of these features. Conclusions: We interpret the CND emission as coming from a hot, thermalized, thin layer at the surface of the clouds. The observed H2 corresponds only to a small fraction of the total H2 mass. The emission remains fairly strong in the whole central cavity, but it is not thermalized. A strong deviation from thermal equilibrium is detected near the minicavity. We suggest that this emission is caused by constantly forming H2 that is destroyed again before it reaches ortho/para equilibrium.

  2. A mechanistic approach to explore novel HDAC1 inhibitor using pharmacophore modeling, 3D- QSAR analysis, molecular docking, density functional and molecular dynamics simulation study.

    PubMed

    Choubey, Sanjay K; Jeyaraman, Jeyakanthan

    2016-11-01

    Deregulated epigenetic activity of Histone deacetylase 1 (HDAC1) in tumor development and carcinogenesis pronounces it as promising therapeutic target for cancer treatment. HDAC1 has recently captured the attention of researchers owing to its decisive role in multiple types of cancer. In the present study a multistep framework combining ligand based 3D-QSAR, molecular docking and Molecular Dynamics (MD) simulation studies were performed to explore potential compound with good HDAC1 binding affinity. Four different pharmacophore hypotheses Hypo1 (AADR), Hypo2 (AAAH), Hypo3 (AAAR) and Hypo4 (ADDR) were obtained. The hypothesis Hypo1 (AADR) with two hydrogen bond acceptors (A), one hydrogen bond donor (D) and one aromatics ring (R) was selected to build 3D-QSAR model on the basis of statistical parameter. The pharmacophore hypothesis produced a statistically significant QSAR model, with co-efficient of correlation r(2)=0.82 and cross validation correlation co-efficient q(2)=0.70. External validation result displays high predictive power with r(2) (o) value of 0.88 and r(2) (m) value of 0.58 to carry out further in silico studies. Virtual screening result shows ZINC70450932 as the most promising lead where HDAC1 interacts with residues Asp99, His178, Tyr204, Phe205 and Leu271 forming seven hydrogen bonds. A high docking score (-11.17kcal/mol) and lower docking energy -37.84kcal/mol) displays the binding efficiency of the ligand. Binding free energy calculation was done using MM/GBSA to access affinity of ligands towards protein. Density Functional Theory was employed to explore electronic features of the ligands describing intramolcular charge transfer reaction. Molecular dynamics simulation studies at 50ns display metal ion (Zn)-ligand interaction which is vital to inhibit the enzymatic activity of the protein.

  3. Molecular modeling study of CP-690550 derivatives as JAK3 kinase inhibitors through combined 3D-QSAR, molecular docking, and dynamics simulation techniques.

    PubMed

    Wang, Jing Li; Cheng, Li Ping; Wang, Tian Chi; Deng, Wei; Wu, Fan Hong

    2017-03-01

    To develop more potent JAK3 kinase inhibitors, a series of CP-690550 derivatives were investigated using combined molecular modeling techniques, such as 3D-QSAR, molecular docking and molecular dynamics (MD). The leave-one-out correlation (q(2)) and non-cross-validated correlation coefficient (r(2)) of the best CoMFA model are 0.715 and 0.992, respectively. The q(2) and r(2) values of the best CoMSIA model are 0.739 and 0.995, respectively. The steric, electrostatic, and hydrophobic fields played important roles in determining the inhibitory activity of CP-690550 derivatives. Some new JAK3 kinase inhibitors were designed. Some of them have better inhibitory activity than the most potent Tofacitinib (CP-690550). Molecular docking was used to identify some key amino acid residues at the active site of JAK3 protein. 10ns MD simulations were successfully performed to confirm the detailed binding mode and validate the rationality of docking results. The calculation of the binding free energies by MMPBSA method gives a good correlation with the predicted biological activity. To our knowledge, this is the first report on MD simulations and free energy calculations for this series of compounds. The combination results of this study will be valuable for the development of potent and novel JAK3 kinase inhibitors.

  4. In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations.

    PubMed

    Gao, Xiaodong; Han, Liping; Ren, Yujie

    2016-05-05

    Checkpoint kinase 1 (Chk1) is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q² values (0.531, 0.726), fitted correlation r² coefficients (higher than 0.90), and standard error of prediction (less than 0.250). These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity.

  5. Novel use of chemical shift in NMR as molecular descriptor: a first report on modeling carbonic anhydrase inhibitory activity and related parameters.

    PubMed

    Khadikar, Padmakar V; Sharma, Vimukta; Karmarkar, Sneha; Supuran, Claudiu T

    2005-02-15

    A novel use of NMR chemical shift of the SO(2)NH(2) protons (in dioxane as solvent) as a molecular descriptor is described for modeling the inhibition constant for benzene sulfonamides against the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The methodology is extended to model diuretic activity and lipophilicity of benzene sulfonamide derivatives. The regression analysis of the data has shown that the NMR chemical shift is incapable of modeling lipophilicity. However, it is quite useful for modeling the diuretic activity of these derivatives. The results are compared with those obtained using distance-based topological indices: Wiener (W)-, Szeged (Sz)-, and PI (Padmakar-Ivan) indices.

  6. Studies of new fused benzazepine as selective dopamine D3 receptor antagonists using 3D-QSAR, molecular docking and molecular dynamics.

    PubMed

    Liu, Jing; Li, Yan; Zhang, Shuwei; Xiao, Zhengtao; Ai, Chunzhi

    2011-02-18

    In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 collected benzazepine (BAZ) DA D3 antagonists with diverse kinds of structures, a variety of in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), homology modeling, molecular docking and molecular dynamics (MD) were carried out to reveal the requisite 3D structural features for activity. Our results show that both the receptor-based (Q(2) = 0.603, R(2) (ncv) = 0.829, R(2) (pre) = 0.690, SEE = 0.316, SEP = 0.406) and ligand-based 3D-QSAR models (Q(2) = 0.506, R(2) (ncv) =0.838, R(2) (pre) = 0.794, SEE = 0.316, SEP = 0.296) are reliable with proper predictive capacity. In addition, a combined analysis between the CoMFA, CoMSIA contour maps and MD results with a homology DA receptor model shows that: (1) ring-A, position-2 and R(3) substituent in ring-D are crucial in the design of antagonists with higher activity; (2) more bulky R(1) substituents (at position-2 of ring-A) of antagonists may well fit in the binding pocket; (3) hydrophobicity represented by MlogP is important for building satisfactory QSAR models; (4) key amino acids of the binding pocket are CYS101, ILE105, LEU106, VAL151, PHE175, PHE184, PRO254 and ALA251. To our best knowledge, this work is the first report on 3D-QSAR modeling of the new fused BAZs as DA D3 antagonists. These results might provide information for a better understanding of the mechanism of antagonism and thus be helpful in designing new potent DA D3 antagonists.

  7. Molecular Modeling Studies of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors through Receptor-Based 3D-QSAR and Molecular Dynamics Simulations.

    PubMed

    Qian, Haiyan; Chen, Jiongjiong; Pan, Youlu; Chen, Jianzhong

    2016-09-19

    11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a potential target for the treatment of numerous human disorders, such as diabetes, obesity, and metabolic syndrome. In this work, molecular modeling studies combining molecular docking, 3D-QSAR, MESP, MD simulations and free energy calculations were performed on pyridine amides and 1,2,4-triazolopyridines as 11β-HSD1 inhibitors to explore structure-activity relationships and structural requirement for the inhibitory activity. 3D-QSAR models, including CoMFA and CoMSIA, were developed from the conformations obtained by docking strategy. The derived pharmacophoric features were further supported by MESP and Mulliken charge analyses using density functional theory. In addition, MD simulations and free energy calculations were employed to determine the detailed binding process and to compare the binding modes of inhibitors with different bioactivities. The binding free energies calculated by MM/PBSA showed a good correlation with the experimental biological activities. Free energy analyses and per-residue energy decomposition indicated the van der Waals interaction would be the major driving force for the interactions between an inhibitor and 11β-HSD1. These unified results may provide that hydrogen bond interactions with Ser170 and Tyr183 are favorable for enhancing activity. Thr124, Ser170, Tyr177, Tyr183, Val227, and Val231 are the key amino acid residues in the binding pocket. The obtained results are expected to be valuable for the rational design of novel potent 11β-HSD1 inhibitors.

  8. Molecular Cloning and 3D Structure Modeling of APEX1, DNA Base Excision Repair Enzyme from the Camel, Camelus dromedarius

    PubMed Central

    Ataya, Farid Shokry; Fouad, Dalia; Malik, Ajamaluddin; Saeed, Hesham Mahmoud

    2012-01-01

    The domesticated one-humped camel, Camelus dromedarius, is one of the most important animals in the Arabian Desert. It is exposed most of its life to both intrinsic and extrinsic genotoxic factors that are known to cause gross DNA alterations in many organisms. Ionic radiation and sunlight are known producers of Reactive Oxygen Species (ROS), one of the causes for DNA lesions. The damaged DNA is repaired by many enzymes, among of them Base Excision Repair enzymes, producing the highly mutagenic apurinic/apyrimidinicsites (AP sites). Therefore, recognition of AP sites is fundamental to cell/organism survival. In the present work, the full coding sequence of a putative cAPEX1 gene was amplified for the first time from C. dromedarius by RT-PCR and cloned (NCBI accession number are HM209828 and ADJ96599 for nucleotides and amino acids, respectively). cDNA sequencing was deduced to be 1041 nucleotides, of which 954 nucleotides encode a protein of 318 amino acids, similar to the coding region of the APEX1 gene and the protein from many other species. The calculated molecular weight and isoelectric point of cAPEX1 using Bioinformatics tools was 35.5 kDa and 8.11, respectively. The relative expressions of cAPEX1 in camel kidney, spleen, lung and testis were examined using qPCR and compared with that of the liver using a 18S ribosomal subunit as endogenous control. The highest level of cAPEX1 transcript was found in the testis; 325% higher than the liver, followed by spleen (87%), kidney (20%) and lung (5%), respectively. The cAPEX1 is 94%–97% similar to their mammalian counterparts. Phylogenetic analysis revealed that cAPEX1 is grouped together with that of S. scrofa. The predicted 3D structure of cAPEX1 has similar folds and topology with the human (hAPEX1). The root-mean-square deviation (rmsd) between cAPEX1 and hAPEX1 was 0.582 and the Q-score was 0.939. PMID:22942721

  9. Design and evaluation of the variable-angle slant-hole collimator for 3D molecular breast imaging

    NASA Astrophysics Data System (ADS)

    Gopan, Olga

    Purpose: The purpose of this work is to develop an improved method for 3D molecular imaging of the breast using limited angle SPECT. Methods: The proposed method uses a variable-angle slant-hole (VASH) collimator. Rather than rotate the camera around the breast, the VASH collimator allows limited angle, tomographic acquisition while the detector remains stationary and flush against the compression paddle. This design minimizes object-to-detector distance for high spatial resolution. Theoretical analysis is presented of VASH spatial resolution and sensitivity, including depth-of-interaction (DOI) effects and magnification. The theory is compared with Monte Carlo simulation results for a point source, a breast phantom including a compression paddle and a realistically segmented breast phantom with an inhomogeneous background uptake. A channelized Hotelling observer is applied to the evaluation of VASH using a lesion detection task, and the standard areaunder- the-curve (AUC) metric is obtained. Experimental results are presented using a proof-of-concept VASH collimator constructed of brass and used to image a low energy, Am-241 source. Results: The theoretical model of the VASH system showed good agreement with Monte Carlo simulations based on spatial resolution, including DOI effects, and sensitivity. The DOI effect resulted in roughly a 2 mm loss in spatial resolution only in depth dimension; in the other two dimensions the spatial resolution was not affected by DOI. In terms of contrast-to-noise ratio (CNR) and AUC, VASH outperformed a parallel hole SPECT approach. In terms of CNR, VASH outperformed a planar approach when the background inhomogeneity level was greater than 20% and in discerning two overlapping lesions. The difference in VASH and planar AUCs was not statistically significant. The reconstructed images from the proof-of-concept VASH collimator demonstrated the expected image blur in the depth dimension due to limited projection angle effects

  10. Allosteric pathway identification through network analysis: from molecular dynamics simulations to interactive 2D and 3D graphs.

    PubMed

    Allain, Ariane; Chauvot de Beauchêne, Isaure; Langenfeld, Florent; Guarracino, Yann; Laine, Elodie; Tchertanov, Luba

    2014-01-01

    Allostery is a universal phenomenon that couples the information induced by a local perturbation (effector) in a protein to spatially distant regulated sites. Such an event can be described in terms of a large scale transmission of information (communication) through a dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally frustrated) clusters of residues. To elaborate a rational description of allosteric coupling, we propose an original approach - MOdular NETwork Analysis (MONETA) - based on the analysis of inter-residue dynamical correlations to localize the propagation of both structural and dynamical effects of a perturbation throughout a protein structure. MONETA uses inter-residue cross-correlations and commute times computed from molecular dynamics simulations and a topological description of a protein to build a modular network representation composed of clusters of residues (dynamic segments) linked together by chains of residues (communication pathways). MONETA provides a brand new direct and simple visualization of protein allosteric communication. A GEPHI module implemented in the MONETA package allows the generation of 2D graphs of the communication network. An interactive PyMOL plugin permits drawing of the communication pathways between chosen protein fragments or residues on a 3D representation. MONETA is a powerful tool for on-the-fly display of communication networks in proteins. We applied MONETA for the analysis of communication pathways (i) between the main regulatory fragments of receptors tyrosine kinases (RTKs), KIT and CSF-1R, in the native and mutated states and (ii) in proteins STAT5 (STAT5a and STAT5b) in the phosphorylated and the unphosphorylated forms. The description of the physical support for allosteric coupling by MONETA allowed a comparison of the mechanisms of (a) constitutive activation induced by equivalent mutations in two RTKs and (b) allosteric regulation in the activated and non

  11. Application of the quantum mechanical IEF/PCM-MST hydrophobic descriptors to selectivity in ligand binding.

    PubMed

    Ginex, Tiziana; Muñoz-Muriedas, Jordi; Herrero, Enric; Gibert, Enric; Cozzini, Pietro; Luque, F Javier

    2016-06-01

    We have recently reported the development and validation of quantum mechanical (QM)-based hydrophobic descriptors derived from the parametrized IEF/PCM-MST continuum solvation model for 3D-QSAR studies within the framework of the Hydrophobic Pharmacophore (HyPhar) method. In this study we explore the applicability of these descriptors to the analysis of selectivity fields. To this end, we have examined a series of 88 compounds with inhibitory activities against thrombin, trypsin and factor Xa, and the HyPhar results have been compared with 3D-QSAR models reported in the literature. The quantitative models obtained by combining the electrostatic and non-electrostatic components of the octanol/water partition coefficient yield results that compare well with the predictive potential of standard CoMFA and CoMSIA techniques. The results also highlight the potential of HyPhar descriptors to discriminate the selectivity of the compounds against thrombin, trypsin, and factor Xa. Moreover, the graphical representation of the hydrophobic maps provides a direct linkage with the pattern of interactions found in crystallographic structures. Overall, the results support the usefulness of the QM/MST-based hydrophobic descriptors as a complementary approach for disclosing structure-activity relationships in drug design and for gaining insight into the molecular determinants of ligand selectivity. Graphical Abstract Quantum Mechanical continuum solvation calculations performed with the IEF/PCM-MST method are used to derived atomic hydrophobic descriptors, which are then used to discriminate the selectivity of ligands against thrombin, trypsin and factor Xa. The descriptors provide complementary view to standard 3D-QSAR analysis, leading to a more comprehensive understanding of ligand recognition.

  12. A Bayesian network model for predicting aquatic toxicity mode of action using two dimensional theoretical molecular descriptors.

    PubMed

    Carriger, John F; Martin, Todd M; Barron, Mace G

    2016-11-01

    The mode of toxic action (MoA) has been recognized as a key determinant of chemical toxicity, but development of predictive MoA classification models in aquatic toxicology has been limited. We developed a Bayesian network model to classify aquatic toxicity MoA using a recently published dataset containing over one thousand chemicals with MoA assignments for aquatic animal toxicity. Two dimensional theoretical chemical descriptors were generated for each chemical using the Toxicity Estimation Software Tool. The model was developed through augmented Markov blanket discovery from the dataset of 1098 chemicals with the MoA broad classifications as a target node. From cross validation, the overall precision for the model was 80.2%. The best precision was for the AChEI MoA (93.5%) where 257 chemicals out of 275 were correctly classified. Model precision was poorest for the reactivity MoA (48.5%) where 48 out of 99 reactive chemicals were correctly classified. Narcosis represented the largest class within the MoA dataset and had a precision and reliability of 80.0%, reflecting the global precision across all of the MoAs. False negatives for narcosis most often fell into electron transport inhibition, neurotoxicity or reactivity MoAs. False negatives for all other MoAs were most often narcosis. A probabilistic sensitivity analysis was undertaken for each MoA to examine the sensitivity to individual and multiple descriptor findings. The results show that the Markov blanket of a structurally complex dataset can simplify analysis and interpretation by identifying a subset of the key chemical descriptors associated with broad aquatic toxicity MoAs, and by providing a computational chemistry-based network classification model with reasonable prediction accuracy.

  13. Molecular modeling studies on series of Btk inhibitors using docking, structure-based 3D-QSAR and molecular dynamics simulation: a combined approach.

    PubMed

    Balasubramanian, Pavithra K; Balupuri, Anand; Cho, Seung Joo

    2016-03-01

    Bruton tyrosine kinase (Btk) is a non-receptor tyrosine kinase. It is a crucial component in BCR pathway and expressed only in hematopoietic cells except T cells and Natural killer cells. BTK is a promising target because of its involvement in signaling pathways and B cell diseases such as autoimmune disorders and lymphoma. In this work, a combined molecular modeling study of molecular docking, 3D-QSAR and molecular dynamic (MD) simulation were performed on a series of 2,5-diaminopyrimidine compounds as inhibitors targeting Btk kinase to understand the interaction and key residues involved in the inhibition. A structure based CoMFA (q (2) = 0.675, NOC = 5, r (2) = 0.961) and COMSIA (q (2) = 0.704, NOC = 6, r (2) = 0.962) models were developed from the conformation obtained by docking. The developed models were subjected to various validation techniques such as leave-five-out, external test set, bootstrapping, progressive sampling and rm (2) metrics and found to have a good predictive ability in both internal and external validation. Our docking results showed the important residues that interacts in the active site residues in inhibition of Btk kinase. Furthermore, molecular dynamics simulation was employed to study the stability of the docked conformation and to investigate the binding interactions in detail. The MD simulation analyses identified several important hydrogen bonds with Btk, including the gatekeeper residue Thr474 and Met477 at the hinge region. Hydrogen bond with active site residues Leu408 and Arg525 were also recognized. A good correlation between the MD results, docking studies and the contour map analysis are observed. This indicates that the developed models are reliable. Our results from this study can provide insights in the designing and development of more potent Btk kinase inhibitors.

  14. Sparsity-based Ankylography for Recovering 3D molecular structures from single-shot 2D scattered light intensity

    PubMed Central

    Mutzafi, Maor; Shechtman, Yoav; Eldar, Yonina C.; Cohen, Oren; Segev, Mordechai

    2015-01-01

    Deciphering the three-dimensional (3D) structure of complex molecules is of major importance, typically accomplished with X-ray crystallography. Unfortunately, many important molecules cannot be crystallized, hence their 3D structure is unknown. Ankylography presents an alternative, relying on scattering an ultrashort X-ray pulse off a single molecule before it disintegrates, measuring the far-field intensity on a two-dimensional surface, followed by computation. However, significant information is absent due to lower dimensionality of the measurements and the inability to measure the phase. Recent Ankylography experiments attracted much interest, but it was counter-argued that Ankylography is valid only for objects containing a small number of volume pixels. Here, we propose a sparsity-based approach to reconstruct the 3D structure of molecules. Sparsity is natural for Ankylography, because molecules can be represented compactly in stoichiometric basis. Utilizing sparsity, we surpass current limits on recoverable information by orders of magnitude, paving the way for deciphering the 3D structure of macromolecules. PMID:26289358

  15. Increasing 3D Supramolecular Order by Decreasing Molecular Order. A Comparative Study of Helical Assemblies of Dendronized Nonchlorinated and Tetrachlorinated Perylene Bisimides.

    PubMed

    Partridge, Benjamin E; Leowanawat, Pawaret; Aqad, Emad; Imam, Mohammad R; Sun, Hao-Jan; Peterca, Mihai; Heiney, Paul A; Graf, Robert; Spiess, Hans W; Zeng, Xiangbing; Ungar, Goran; Percec, Virgil

    2015-04-22

    A nonplanar, twisted, and flexible tetrachlorinated perylene bisimide (Cl4PBI) was functionalized with two AB3 minidendrons containing hydrogenated or semifluorinated dodecyl groups. The hydrogenated dendron was attached to the imide groups of Cl4PBI via m = 0, 1, and 2 methylenic units, whereas the dendron containing semifluorinated groups was attached via m = 3 or a di(ethylene oxide) linker (m = 2EO). The supramolecular structures of these compounds, determined by a combination of differential scanning calorimetry, X-ray diffraction, and solid-state NMR, were compared with those of nonchlorinated planar and rigid PBI reported previously, which demonstrated the thermodynamically controlled formation of 2D periodic arrays at high temperatures and 3D arrays at low temperatures. The molecularly less ordered Cl4PBI containing hydrogenated dendrons self-organize into exclusively 3D crystalline periodic arrays under thermodynamic control for m = 0 and 2, while the more highly molecularly ordered PBI produced less stable and ordered 3D crystals and also 2D assemblies. This induction of a higher degree of 3D order in supramolecular assemblies of the less well-ordered molecular building blocks was unanticipated. The semifluorinated dendronized Cl4PBI with m = 3 formed a 2D columnar hexagonal array under kinetic control, whereas the compound with m = 2EO formed an unusual 2D honeycomb-like hexagonal phase under thermodynamic control. These Cl4PBI compounds provide a new route to stable crystalline assemblies via thermodynamic control at lower temperatures than previously obtained with PBI, thus generating 3D order in an accessible range of temperature of interest for structural analysis and for technological applications.

  16. Atom pair 2D-fingerprints perceive 3D-molecular shape and pharmacophores for very fast virtual screening of ZINC and GDB-17.

    PubMed

    Awale, Mahendra; Reymond, Jean-Louis

    2014-07-28

    Three-dimensional (3D) molecular shape and pharmacophores are important determinants of the biological activity of organic molecules; however, a precise computation of 3D-shape is generally too slow for virtual screening of very large databases. A reinvestigation of the concept of atom pairs initially reported by Carhart et al. and extended by Schneider et al. showed that a simple atom pair fingerprint (APfp) counting atom pairs at increasing topological distances in 2D-structures without atom property assignment correlates with various representations of molecular shape extracted from the 3D-structures. A related 55-dimensional atom pair fingerprint extended with atom properties (Xfp) provided an efficient pharmacophore fingerprint with good performance for ligand-based virtual screening such as the recovery of active compounds from decoys in DUD, and overlap with the ROCS 3D-pharmacophore scoring function. The APfp and Xfp data were organized for web-based extremely fast nearest-neighbor searching in ZINC (13.5 M compounds) and GDB-17 (50 M random subset) freely accessible at www.gdb.unibe.ch .

  17. Free energy force field (FEFF) 3D-QSAR analysis of a set of Plasmodium falciparum dihydrofolate reductase inhibitors

    NASA Astrophysics Data System (ADS)

    Santos-Filho, Osvaldo A.; Mishra, Rama K.; Hopfinger, A. J.

    2001-09-01

    Free energy force field (FEFF) 3D-QSAR analysis was used to construct ligand-receptor binding models for a set of 18 structurally diverse antifolates including pyrimethamine, cycloguanil, methotrexate, aminopterin and trimethoprim, and 13 pyrrolo[2,3-d]pyrimidines. The molecular target (`receptor') used was a 3D-homology model of a specific mutant type of Plasmodium falciparum (Pf) dihydrofolate reductase (DHFR). The dependent variable of the 3D-QSAR models is the IC50 inhibition constant for the specific mutant type of PfDHFR. The independent variables of the 3D-QSAR models (the descriptors) are scaled energy terms of a modified first-generation AMBER force field combined with a hydration shell aqueous solvation model and a collection of 2D-QSAR descriptors often used in QSAR studies. Multiple temperature molecular dynamics simulation (MDS) and the genetic function approximation (GFA) were employed using partial least square (PLS) and multidimensional linear regressions as the fitting functions to develop FEFF 3D-QSAR models for the binding process. The significant FEFF energy terms in the best 3D-QSAR models include energy contributions of the direct ligand-receptor interaction. Some changes in conformational energy terms of the ligand due to binding to the enzyme are also found to be important descriptors. The FEFF 3D-QSAR models indicate some structural features perhaps relevant to the mechanism of resistance of the PfDHFR to current antimalarials. The FEFF 3D-QSAR models are also compared to receptor-independent (RI) 4D-QSAR models developed in an earlier study and subsequently refined using recently developed generalized alignment rules.

  18. Molecular tectonics: pyridyl containing thiacalix[4]arene based tectons for the generation of 2- and 3-D silver coordination networks.

    PubMed

    Ovsyannikov, A; Lang, M N; Ferlay, S; Solovieva, S E; Antipin, I S; Konovalov, A I; Kyritsakas, N; Hosseini, M W

    2013-01-07

    Three new organic tectons (2–4) based on the p-tert-butylthiacalix[4]arene backbone, blocked in the 1,3-alternate conformation, bearing four pyridyl coordinating moieties, have been synthesised and characterised in the solid state. The ligands are positional isomers and differ by the position of the N atom on the pyridyl unit (ortho for 2, meta for 3 and para for 4). Their combination with the Ag+ cation leads, reproducibly, to the formation of 2- and 3-D infinite silver coordination networks. Independent of the nature of the anion, the combination of 2 offering four (N,S) type chelates with the Ag+ cation affords an unprecedented diamond type 3D network. Both 3 and 4, behaving as tetrakis monodentate ligands, lead to the formation of 2-D architectures.

  19. A New Approach for Investigating the Molecular Recognition of Protein: Toward Structure-Based Drug Design Based on the 3D-RISM Theory.

    PubMed

    Kiyota, Yasuomi; Yoshida, Norio; Hirata, Fumio

    2011-11-08

    A new approach to investigate a molecular recognition process of protein is presented based on the three-dimensional reference interaction site model (3D-RISM) theory, a statistical mechanics theory of molecular liquids. Numerical procedure for solving the conventional 3D-RISM equation consists of two steps. In step 1, we solve ordinary RISM (or 1D-RISM) equations for a solvent mixture including target ligands in order to obtain the density pair correlation functions (PCF) among molecules in the solution. Then, we solve the 3D-RISM equation for a solute-solvent system to find three-dimensional density distribution functions (3D-DDF) of solvent species around a protein, using PCF obtained in the first step. A key to the success of the method was to regard a target ligand as one of "solvent" species. However, the success is limited due to a difficulty of solving the 1D-RISM equation for a solvent mixture, including large ligand molecules. In the present paper, we propose a method which eases the limitation concerning solute size in the conventional method. In this approach, we solve a solute-solute 3D-RISM equations for a protein-ligand system in which both proteins and ligands are regarded as "solutes" at infinite dilution. The 3D- and 1D-RISM equations are solved for protein-solvent and ligand-solvent systems, respectively, in order to obtain the 3D- and 1D-DDF of solvent around the solutes, which are required for solving the solute-solute 3D-RISM equation. The method is applied to two practical and noteworthy examples concerning pharmaceutical design. One is an odorant binding protein in the Drosophila melanogaster , which binds an ethanol molecule. The other is phospholipase A2, which is known as a receptor of acetylsalicylic acid or aspirin. The result indicates that the method successfully reproduces the binding mode of the ligand molecules in the binding sites measured by the experiments.

  20. 3D Molecular Modelling Study of the H7N9 RNA-Dependent RNA Polymerase as an Emerging Pharmacological Target

    PubMed Central

    Vlachakis, Dimitrios

    2013-01-01

    Currently not much is known about the H7N9 strain, and this is the major drawback for a scientific strategy to tackle this virus. Herein, the 3D complex structure of the H7N9 RNA-dependent RNA polymerase has been established using a repertoire of molecular modelling techniques including homology modelling, molecular docking, and molecular dynamics simulations. Strikingly, it was found that the oligonucleotide cleft and tunnel in the H7N9 RNA-dependent RNA polymerase are structurally very similar to the corresponding region on the hepatitis C virus RNA-dependent RNA polymerase crystal structure. A direct comparison and a 3D postdynamics analysis of the 3D complex of the H7N9 RNA-dependent RNA polymerase provide invaluable clues and insight regarding the role and mode of action of a series of interacting residues on the latter enzyme. Our study provides a novel and efficiently intergraded platform with structural insights for the H7N9 RNA-dependent RNA Polymerase. We propose that future use and exploitation of these insights may prove invaluable in the fight against this lethal, ongoing epidemic. PMID:24187616

  1. In silico study on β-aminoketone derivatives as thyroid hormone receptor inhibitors: a combined 3D-QSAR and molecular docking study.

    PubMed

    Wang, Fang-Fang; Yang, Wei; Shi, Yong-Hui; Le, Guo-Wei

    2016-12-01

    In order to explore the structure-activity correlation of a series of β-aminoketone analogs as inhibitors of thyroid hormone receptor (TR), a set of three-dimensional quantitative structure-activity relationship (3D-QSAR) models based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA), for the first time, were developed in the present work. The best CoMFA model with steric and electrostatic fields exhibited [Formula: see text], [Formula: see text] for TRβ, and [Formula: see text], [Formula: see text] for TRα. 3D contour maps produced from the optimal models were further analyzed individually, which provide the areas in space where interactive fields would affect the inhibitory activity. In addition, the binding modes of inhibitors at the active site of TRs were examined using molecular docking, the results indicated that this series of inhibitors fit into the active site of TRs by forming hydrogen bonding and electrostatic interactions. The docking studies also revealed that Leu305, Val458 for TRβ, and Asp407 for TRα are showing hydrogen bonds with the most active inhibitors. In any case, the 3D-QSAR models combined with the binding information will serve as a useful approach to explore the chemical space for improving the activity of TRβ and TRα inhibitors.

  2. Searching for anthranilic acid-based thumb pocket 2 HCV NS5B polymerase inhibitors through a combination of molecular docking, 3D-QSAR and virtual screening.

    PubMed

    Vrontaki, Eleni; Melagraki, Georgia; Mavromoustakos, Thomas; Afantitis, Antreas

    2016-01-01

    A combination of the following computational methods: (i) molecular docking, (ii) 3-D Quantitative Structure Activity Relationship Comparative Molecular Field Analysis (3D-QSAR CoMFA), (iii) similarity search and (iv) virtual screening using PubChem database was applied to identify new anthranilic acid-based inhibitors of hepatitis C virus (HCV) replication. A number of known inhibitors were initially docked into the "Thumb Pocket 2" allosteric site of the crystal structure of the enzyme HCV RNA-dependent RNA polymerase (NS5B GT1b). Then, the CoMFA fields were generated through a receptor-based alignment of docking poses to build a validated and stable 3D-QSAR CoMFA model. The proposed model can be first utilized to get insight into the molecular features that promote bioactivity, and then within a virtual screening procedure, it can be used to estimate the activity of novel potential bioactive compounds prior to their synthesis and biological tests.

  3. Atom-based 3D-QSAR, molecular docking and molecular dynamics simulation assessment of inhibitors for thyroid hormone receptor α and β.

    PubMed

    Gupta, Manish Kumar; Misra, Krishna

    2014-06-01

    The three-dimensional quantitative structure-activity relationship (3D-QSAR) for inhibitors of thyroid hormone receptors (TR) α and (TR) β was studied. The training set of the TRα model generated a correlation coefficient (R(2)) =  0.9535, with standard deviation (SD) =  0.3016. From the test set of the TRα model, a Q(2) value for the predicted activities (= 0.4303), squared correlation (random selection R(2)-CV  =  0.6929), Pearson-R (= 0.7294) and root mean square error (RMSE  =  0.6342) were calculated. The P-value for TRα (= 1.411e-96) and TRβ (= 2.108e-165) models indicate a high degree of self-reliance. For the TRβ model, the training set yielded R(2) = 0.9424 with SD = 0.3719. From the test set of TRβ, Q(2) value (= 0.5336), the squared correlation (R(2)-CV  =  0.7201), the Pearson-R (= 0.7852) and RMSE for test set predictions (= 0.8630) all strengthen the good predictive competence of the QSAR model derived. Examination of internal as well as external validation supports the rationality and good predictive ability of the best model. Molecular docking explained the conformations of molecules and important amino acid residues at the docking pocket, and a molecular dynamics simulation study further uncovered the binding process and validated the rationality of docking results. The findings not only lead to a better understanding of interactions between these antagonists and thyroid hormone receptors α and β, but also provide valuable information about the impact of structure on activity that will be very beneficial in the design of novel antagonists with preferred activity.

  4. Topology dictionary for 3D video understanding.

    PubMed

    Tung, Tony; Matsuyama, Takashi

    2012-08-01

    This paper presents a novel approach that achieves 3D video understanding. 3D video consists of a stream of 3D models of subjects in motion. The acquisition of long sequences requires large storage space (2 GB for 1 min). Moreover, it is tedious to browse data sets and extract meaningful information. We propose the topology dictionary to encode and describe 3D video content. The model consists of a topology-based shape descriptor dictionary which can be generated from either extracted patterns or training sequences. The model relies on 1) topology description and classification using Reeb graphs, and 2) a Markov motion graph to represent topology change states. We show that the use of Reeb graphs as the high-level topology descriptor is relevant. It allows the dictionary to automatically model complex sequences, whereas other strategies would require prior knowledge on the shape and topology of the captured subjects. Our approach serves to encode 3D video sequences, and can be applied for content-based description and summarization of 3D video sequences. Furthermore, topology class labeling during a learning process enables the system to perform content-based event recognition. Experiments were carried out on various 3D videos. We showcase an application for 3D video progressive summarization using the topology dictionary.

  5. Molecular modeling studies of [6,6,5] Tricyclic Fused Oxazolidinones as FXa inhibitors using 3D-QSAR, Topomer CoMFA, molecular docking and molecular dynamics simulations.

    PubMed

    Xu, Cheng; Ren, Yujie

    2015-10-15

    Coagulation factor Xa (Factor Xa, FXa) is a particularly promising target for novel anticoagulant therapy. The first oral factor Xa inhibitor has been approved in the EU and Canada in 2008. In this work, 38 [6,6,5] Tricyclic Fused Oxazolidinones were studied using a combination of molecular modeling techniques including three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, molecular dynamics and Topomer CoMFA (comparative molecular field analysis) were used to build 3D-QSAR models. The results show that the best CoMFA model has q(2)=0.511 and r(2)=0.984, the best CoMSIA (comparative molecular similarity indices analysis) model has q(2)=0.700 and r(2)=0.993 and the Topomer CoMFA analysis has q(2)=0.377 and r(2)=0.886. The results indicated the steric, hydrophobic, H-acceptor and electrostatic fields play key roles in models. Molecular docking and molecular dynamics explored the binding relationship of the ligand and the receptor protein.

  6. COMPARATIVE STUDY OF THREE FUNDAMENTAL ORGANIC COMPOUNDS OF CHAIN STRUCTURE OF THREE RINGS An approach based in the molecular descriptors of the DFT (Density Functional Theory)

    NASA Astrophysics Data System (ADS)

    Leon, Neira B. Oscar; Fabio, Mejía Elio; Elizabeth, y. Rincón B.

    2008-04-01

    The organic molecules of a chain structure containing phenyl, oxazole and oxadiazole rings are used in different combinations as active media for tunable lasers. From this viewpoint, we focused in the theoretical study of organic compounds of three rings, which have similar optical properties (fluorescence and laser properties). The main goal of this study is to compare the electronic structure through the analysis of molecular global descriptors defined in the DFT framework of2-[2-X-phenyl]-5-phenyl-1,3-Oxazole, 2-[2-X-phenyl]-5-phenyl-1,3,4-Oxadiazole, and 2-[2-X-phenyl]-5-phenyl-furane with X = H, F and Cl. The basis set used was 6-31G+(d).

  7. Predicting Subtype Selectivity for Adenosine Receptor Ligands with Three-Dimensional Biologically Relevant Spectrum (BRS-3D)

    PubMed Central

    He, Song-Bing; Ben Hu; Kuang, Zheng-Kun; Wang, Dong; Kong, De-Xin

    2016-01-01

    Adenosine receptors (ARs) are potential therapeutic targets for Parkinson’s disease, diabetes, pain, stroke and cancers. Prediction of subtype selectivity is therefore important from both therapeutic and mechanistic perspectives. In this paper, we introduced a shape similarity profile as molecular descriptor, namely three-dimensional biologically relevant spectrum (BRS-3D), for AR selectivity prediction. Pairwise regression and discrimination models were built with the support vector machine methods. The average determination coefficient (r2) of the regression models was 0.664 (for test sets). The 2B-3 (A2B vs A3) model performed best with q2 = 0.769 for training sets (10-fold cross-validation), and r2 = 0.766, RMSE = 0.828 for test sets. The models’ robustness and stability were validated with 100 times resampling and 500 times Y-randomization. We compared the performance of BRS-3D with 3D descriptors calculated by MOE. BRS-3D performed as good as, or better than, MOE 3D descriptors. The performances of the discrimination models were also encouraging, with average accuracy (ACC) 0.912 and MCC 0.792 (test set). The 2A-3 (A2A vs A3) selectivity discrimination model (ACC = 0.882 and MCC = 0.715 for test set) outperformed an earlier reported one (ACC = 0.784). These results demonstrated that, through multiple conformation encoding, BRS-3D can be used as an effective molecular descriptor for AR subtype selectivity prediction. PMID:27812030

  8. Predicting Subtype Selectivity for Adenosine Receptor Ligands with Three-Dimensional Biologically Relevant Spectrum (BRS-3D)

    NASA Astrophysics Data System (ADS)

    He, Song-Bing; Ben Hu; Kuang, Zheng-Kun; Wang, Dong; Kong, De-Xin

    2016-11-01

    Adenosine receptors (ARs) are potential therapeutic targets for Parkinson’s disease, diabetes, pain, stroke and cancers. Prediction of subtype selectivity is therefore important from both therapeutic and mechanistic perspectives. In this paper, we introduced a shape similarity profile as molecular descriptor, namely three-dimensional biologically relevant spectrum (BRS-3D), for AR selectivity prediction. Pairwise regression and discrimination models were built with the support vector machine methods. The average determination coefficient (r2) of the regression models was 0.664 (for test sets). The 2B-3 (A2B vs A3) model performed best with q2 = 0.769 for training sets (10-fold cross-validation), and r2 = 0.766, RMSE = 0.828 for test sets. The models’ robustness and stability were validated with 100 times resampling and 500 times Y-randomization. We compared the performance of BRS-3D with 3D descriptors calculated by MOE. BRS-3D performed as good as, or better than, MOE 3D descriptors. The performances of the discrimination models were also encouraging, with average accuracy (ACC) 0.912 and MCC 0.792 (test set). The 2A-3 (A2A vs A3) selectivity discrimination model (ACC = 0.882 and MCC = 0.715 for test set) outperformed an earlier reported one (ACC = 0.784). These results demonstrated that, through multiple conformation encoding, BRS-3D can be used as an effective molecular descriptor for AR subtype selectivity prediction.

  9. Molecular docking and 3D-QSAR studies on the binding mechanism of statine-based peptidomimetics with beta-secretase.

    PubMed

    Zuo, Zhili; Luo, Xiaomin; Zhu, Weiliang; Shen, Jianhua; Shen, Xu; Jiang, Hualiang; Chen, Kaixian

    2005-03-15

    beta-Secretase is an important protease in the pathogenesis of Alzheimer's disease. Some statine-based peptidomimetics show inhibitory activities to the beta-secretase. To explore the inhibitory mechanism, molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies on these analogues were performed. The Lamarckian Genetic Algorithm (LGA) was applied to locate the binding orientations and conformations of the peptidomimetics with the beta-secretase. A good correlation between the calculated binding free energies and the experimental inhibitory activities suggests that the identified binding conformations of these potential inhibitors are reliable. Based on the binding conformations, highly predictive 3D-QSAR models were developed with q(2) values of 0.582 and 0.622 for CoMFA and CoMSIA, respectively. The predictive abilities of these models were validated by some compounds that were not included in the training set. Furthermore, the 3D-QSAR models were mapped back to the binding site of the beta-secretase, to get a better understanding of vital interactions between the statine-based peptidomimetics and the protease. Both the CoMFA and the CoMSIA field distributions are in well agreement with the structural characteristics of the binding groove of the beta-secretase. Therefore, the final 3D-QSAR models and the information of the inhibitor-enzyme interaction would be useful in developing new drug leads against Alzheimer's disease.

  10. Low temperature H2S removal with 3-D structural mesoporous molecular sieves supported ZnO from gas stream.

    PubMed

    Li, L; Sun, T H; Shu, C H; Zhang, H B

    2016-07-05

    A series of 3-dimensional (3-D) structural mesoporous silica materials, SBA-16, MCM-48 and KIT-6, was synthesized and supported with different ZnO loadings (10, 20, 30, and 40 wt%) by the incipient wetness method to evaluate the performances on H2S removal at room temperature. These materials were characterized by N2 adsorption, XRD, and TEM to investigate their textural properties. All the ZnO-loaded adsorbents exhibited the H2S removal capacity of bellow 0.1 ppmv. With the best ZnO loading percentage of 30 wt% on MCM-48 and KIT-6, 20 wt% on SBA-16 according to the results of breakthrough test, further increasing ZnO loading caused the decrease of the adsorption capacity due to the agglomeration of ZnO. Besides, the H2S adsorption capacities of the supports materials varied in the order of KIT-6>MCM-48>SBA-16, which was influenced primarily by their pore volume and pore size. With the largest pores in these 3-D arrangement materials, KIT-6 showed the best performance of supported material for ZnO, due to its retained superior physical properties as well as large pore diameter to allow faster gas-solid interaction and huge pore volume to disperse ZnO on the surface of it.

  11. Comprehensive 3D-QSAR and binding mode of BACE-1 inhibitors using R-group search and molecular docking.

    PubMed

    Huang, Dandan; Liu, Yonglan; Shi, Bozhi; Li, Yueting; Wang, Guixue; Liang, Guizhao

    2013-09-01

    The β-enzyme (BACE), which takes an active part in the processing of amyloid precursor protein, thereby leads to the production of amyloid-β (Aβ) in the brain, is a major therapeutic target against Alzheimer's disease. The present study is aimed at studying 3D-QSAR of BACE-1 inhibitors and their binding mode. We build a 3D-QSAR model involving 99 training BACE-1 inhibitors based on Topomer CoMFA, and 26 molecules are employed to validate the external predictive power of the model obtained. The multiple correlation coefficients of fitting modeling, leave one out cross validation, and external validation are 0.966, 0.767 and 0.784, respectively. Topomer search is used as a tool for virtual screening in lead-like compounds of ZINC databases (2012); as a result, we successfully design 30 new molecules with higher activity than that of all training and test inhibitors. Besides, Surflex-dock is employed to explore binding mode of the inhibitors studied when acting with BACE-1 enzyme. The result shows that the inhibitors closely interact with the key sites related to ASP93, THR133, GLN134, ASP289, GLY291, THR292, THR293, ASN294, ARG296 and SER386 of BACE-1.

  12. 3D molecular modeling and evolutionary study of the Trypanosoma brucei DNA Topoisomerase IB, as a new emerging pharmacological target.

    PubMed

    Vlachakis, Dimitrios; Pavlopoulou, Athanasia; Roubelakis, Maria G; Feidakis, Christos; Anagnou, Nikolaos P; Kossida, Sophia

    2014-01-01

    In the present study, an outline is proposed that may lead to specific drug design targeting of the Trypanosoma brucei DNA Topoisomerase IB. In this direction, an unequivocally specific platform was designed for the development of selective modulators. The designed platform is focused on the unique structural and catalytic features of the enzyme. Extensive phylogenetic analysis based on all available published genomes indicated a broad distribution of DNA topoisomerases across eukaryotic species and revealed structurally important amino acids which could be assigned as potentially strong contributors to the regulation of the mechanism of the T. brucei DNA Topoisomerase IB. Based on the above, we propose a comprehensive in silico 3D model for the structure of the T. brucei DNA Topoisomerase IB. Our approach provides an efficient intergraded platform with both evolutionary and structural insights for the rational design of pharmacophore models as well as novel modulators as the anti-T. brucei DNA Topoisomerase IB agents with therapeutic potential.

  13. Study of the molecular gas in the central parsec of the Galaxy through regularized 3D spectroscopy

    NASA Astrophysics Data System (ADS)

    Ciurlo, A.; Paumard, T.; Rouan, D.; Clénet, Y.

    2014-05-01

    The cool gas in the central parsec of the Galaxy is organized in the surrounding circumnuclear disk, made of neutral gas, and the internal minispiral, composed of dust and ionized gas. In order to study the transition between them we have investigated the presence of H2 neutral gas in this area, through NIR spectro-imaging data observed with SPIFFI. To preserve the spatial resolution we implemented a new method consisting of a regularized 3D fit. We concentrated on the supposedly fully ionized central cavity and the very inner edge of the CND. H2 is detected everywhere: at the boundary of the CND and in the central cavity, where it seems to split in two components, one in the background of the minispiral and one inside the Northern arm.

  14. Synthesis, spectral characterization and 3D molecular modeling of some novel nickel(II) complexes derived from 4-aminoantipyrine

    NASA Astrophysics Data System (ADS)

    Nair, M. L. Harikumaran; Lalitha, K. P.

    2014-10-01

    Some novel Ni(II) complexes with the ligand (z)-4-((2-hydroxy-4-methoxyphenyl)diazenyl)-1,5-dimethyl-2-phenyl-1H-pyrazole-3(2H)-one, 3-methoxy phenol azoantipyrine, L having the formulae [Ni(L)2X2] and [Ni(L)2(Y)Cl] where X = 450 Cl-/NO3; Y = NCS- were synthesized and characterized by elemental analysis, molar conductance measurements, magnetic susceptibility measurements, spectral (IR, UV-Visible, EPR, FAB-mass) studies, thermo gravimetric analysis and by TEM image. Energy minimized configuration of the complex [Ni(L)2Cl2] was made with CHEM Bio 3D Ultra 11.0 and the respective parameters were computed. The ligand and the complex [Ni(L)2(Y)Cl] were screened for their antibacterial activities. An octahedral structure is tentatively proposed for the complexes.

  15. Internally defined distances in 3D-quantitative structure-activity relationships

    NASA Astrophysics Data System (ADS)

    Klein, Christian Th.; Kaiblinger, Norbert; Wolschann, Peter

    2002-02-01

    A new type of 3D-QSAR descriptors is introduced. For each molecule under consideration an internal coordinate system is defined relative to molecular points, such as positions of atoms in the molecule or centers of mass or certain substructures. From the origin of this system distances to the solvent accessible surface are calculated at defined spherical coordinate angles, θ and φ. The distances represent steric features, while the molecular electrostatic potentials at the intersection points with the surface represent the electrostatic contributions. The approach is called IDA (internal distances analysis). Matrices obtained by varying the spherical coordinate angles by fixed increments are correlated with the biological activity by partial least squares (PLS). The descriptors, tested with the benchmark steroids and an also well characterized benzodiazepine data set, turn out to be highly predictive. Additionally, they share the advantage of grid-based methods that the obtained models can be visualized, and thus be directly used in a rational drug design approach.

  16. 3D-QSAR, homology modeling, and molecular docking studies on spiropiperidines analogues as agonists of nociceptin/orphanin FQ receptor.

    PubMed

    Liu, Ming; He, Lin; Hu, Xiaopeng; Liu, Peiqing; Luo, Hai-Bin

    2010-12-01

    The nociceptin/orphanin FQ receptor (NOP) has been implicated in a wide range of biological functions, including pain, anxiety, depression and drug abuse. Especially, its agonists have a great potential to be developed into anxiolytics. However, the crystal structure of NOP is still not available. In the present work, both structure-based and ligand-based modeling methods have been used to achieve a comprehensive understanding on 67N-substituted spiropiperidine analogues as NOP agonists. The comparative molecular-field analysis method was performed to formulate a reasonable 3D-QSAR model (cross-validated coefficient q(2)=0.819 and conventional r(2)=0.950), whose robustness and predictability were further verified by leave-eight-out, Y-randomization, and external test-set validations. The excellent performance of CoMFA to the affinity differences among these compounds was attributed to the contributions of electrostatic/hydrogen-bonding and steric/hydrophobic interactions, which was supported by the Surflex-Dock and CDOCKER molecular-docking simulations based on the 3D model of NOP built by the homology modeling method. The CoMFA contour maps and the molecular docking simulations were integrated to propose a binding mode for the spiropiperidine analogues at the binding site of NOP.

  17. 3D-QSAR and molecular docking studies on derivatives of MK-0457, GSK1070916 and SNS-314 as inhibitors against Aurora B kinase.

    PubMed

    Zhang, Baidong; Li, Yan; Zhang, Huixiao; Ai, Chunzhi

    2010-11-02

    Development of anticancer drugs targeting Aurora B, an important member of the serine/threonine kinases family, has been extensively focused on in recent years. In this work, by applying an integrated computational method, including comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), homology modeling and molecular docking, we investigated the structural determinants of Aurora B inhibitors based on three different series of derivatives of 108 molecules. The resultant optimum 3D-QSAR models exhibited (q(2) = 0.605, r(2) (pred) = 0.826), (q(2) = 0.52, r(2) (pred) = 0.798) and (q(2) = 0.582, r(2) (pred) = 0.971) for MK-0457, GSK1070916 and SNS-314 classes, respectively, and the 3D contour maps generated from these models were analyzed individually. The contour map analysis for the MK-0457 model revealed the relative importance of steric and electrostatic effects for Aurora B inhibition, whereas, the electronegative groups with hydrogen bond donating capacity showed a great impact on the inhibitory activity for the derivatives of GSK1070916. Additionally, the predictive model of the SNS-314 class revealed the great importance of hydrophobic favorable contour, since hydrophobic favorable substituents added to this region bind to a deep and narrow hydrophobic pocket composed of residues that are hydrophobic in nature and thus enhanced the inhibitory activity. Moreover, based on the docking study, a further comparison of the binding modes was accomplished to identify a set of critical residues that play a key role in stabilizing the drug-target interactions. Overall, the high level of consistency between the 3D contour maps and the topographical features of binding sites led to our identification of several key structural requirements for more potency inhibitors. Taken together, the results will serve as a basis for future drug development of inhibitors against Aurora B kinase for various tumors.

  18. Modeling and predicting pKa values of mono-hydroxylated polychlorinated biphenyls (HO-PCBs) and polybrominated diphenyl ethers (HO-PBDEs) by local molecular descriptors.

    PubMed

    Yu, Haiying; Wondrousch, Dominik; Yuan, Quan; Lin, Hongjun; Chen, Jianrong; Hong, Huachang; Schüürmann, Gerrit

    2015-11-01

    Hydroxylated polychlorinated biphenyls (HO-PCBs) and polybrominated diphenyl ethers (HO-PBDEs) are attracting considerable concerns because of their multiple endocrine-disrupting effects and wide existence in environment and organisms. The hydroxyl groups enable these chemicals to be ionizable, and dissociation constant, pKa, becomes an important parameter for investigating their environmental behavior and biological activities. In this study, a new pKa prediction model was developed using local molecular descriptors. The dataset contains 21 experimental pKa values of HO-PCBs and HO-PBDEs. The optimized geometries by ab initio HF/6-31G(∗∗) algorithm were used to calculate the site-specific molecular readiness to accept or donate electron charges. The developed model obtained good statistical performance, which significantly outperformed commercial software ACD and SPARC. Mechanism analysis indicates that pKa values increase with the charge-limited donor energy EQocc on hydroxyl oxygen atom and decrease with the energy-limited acceptor charge QEvac on hydroxyl hydrogen atom. The regression model was also applied to calculate pKa values for all 837 mono-hydroxylated PCBs and PBDEs in each class, aiming to provide basic data for the ecological risk assessment of these chemicals.

  19. Compound-class specific estimation of solid organic compound vapour pressure and aqueous solubility from simple molecular structure descriptors and the temperature of melting.

    PubMed

    van Noort, Paul C M

    2009-10-01

    For many solid organic compounds, experimental data for their aqueous solubility and vapour pressure are lacking. Therefore, estimation procedures for these compound properties are needed. On theoretical grounds, this study derives a general compound-class specific estimation procedure for solid organic compound aqueous solubility and vapour pressure. The estimation procedure uses a linear combination of simple molecular descriptors for the molecular structure variation within the compound class and a polynomial for the temperature of melting. This procedure is applied to the vapour pressure of polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs, polychlorinated dibenzo-p-dioxins and biphenyls and to the aqueous solubility of PAHs, methylated PAHs, chlorinated benzenes, polychlorinated and polybrominated biphenyls, chlorinated phenols, cresols, and chlorinated 2-methoxyphenols. The standard error of the solid vapour pressure or aqueous solubility estimates from the various compound-class specific regression equations was about 0.2 log units. For PAHs, chlorobenzenes, and PCBs used in the present study, aqueous solubility estimated from the regression equations taking the temperature of melting equal to 298 K, i.e. assuming that the compounds are in a hypothetical liquid state, was equal, within 0.1-0.3 log units to the subcooled liquid solubility estimated from literature regression equations.

  20. The electronic density obtained from a QTAIM analysis used as molecular descriptor. A study performed in a new series of DHFR inhibitors

    NASA Astrophysics Data System (ADS)

    Tosso, Rodrigo D.; Vettorazzi, Marcela; Andujar, Sebastian A.; Gutierrez, Lucas J.; Garro, Juan C.; Angelina, Emilio; Rodríguez, Ricaurte; Suvire, Fernando D.; Nogueras, Manuel; Cobo, Justo; Enriz, Ricardo D.

    2017-04-01

    The results reported here indicate that the electron density obtained from a QTAIM analysis is an excellent descriptor of molecular interactions that stabilize and destabilize the formation of the ligand-receptor (L-R) complex. The study was conducted on a series of 25 compounds that have inhibitory effects on DHFR. Besides the synthesis and bioassays performed for some of these compounds, various types of molecular calculations were performed. Thus, we performed MD simulations, computations at different levels of theory (ab initio and DFT) using reduced models and a QTAIM study on the different complexes. The resulting model has allowed us to differentiate not only highly active compounds with respect to compounds weakly active, but also among compounds that have similar affinities in this series. The model also showed a high degree of predictability which allows predicting the affinity of non-synthesized compounds. Very important additional information can be obtained through this type of study, it is possible to visualize which amino acids are involved in the interactions determining the different affinities of the ligands.

  1. DDC Descriptor Frequencies.

    ERIC Educational Resources Information Center

    Klingbiel, Paul H.; Jacobs, Charles R.

    This report summarizes the frequency of use of the 7144 descriptors used for indexing technical reports in the Defense Documentation Center (DDC) collection. The descriptors are arranged alphabetically in the first section and by frequency in the second section. The frequency data cover about 427,000 AD documents spanning the interval from March…

  2. 3D-QSAR and molecular docking studies on designing inhibitors of the hepatitis C virus NS5B polymerase

    NASA Astrophysics Data System (ADS)

    Li, Wenlian; Si, Hongzong; Li, Yang; Ge, Cuizhu; Song, Fucheng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

    2016-08-01

    Viral hepatitis C infection is one of the main causes of the hepatitis after blood transfusion and hepatitis C virus (HCV) infection is a global health threat. The HCV NS5B polymerase, an RNA dependent RNA polymerase (RdRp) and an essential role in the replication of the virus, has no functional equivalent in mammalian cells. So the research and development of efficient NS5B polymerase inhibitors provides a great strategy for antiviral therapy against HCV. A combined three-dimensional quantitative structure-activity relationship (QSAR) modeling was accomplished to profoundly understand the structure-activity correlation of a train of indole-based inhibitors of the HCV NS5B polymerase to against HCV. A comparative molecular similarity indices analysis (COMSIA) model as the foundation of the maximum common substructure alignment was developed. The optimum model exhibited statistically significant results: the cross-validated correlation coefficient q2 was 0.627 and non-cross-validated r2 value was 0.943. In addition, the results of internal validations of bootstrapping and Y-randomization confirmed the rationality and good predictive ability of the model, as well as external validation (the external predictive correlation coefficient rext2 = 0.629). The information obtained from the COMSIA contour maps enables the interpretation of their structure-activity relationship. Furthermore, the molecular docking study of the compounds for 3TYV as the protein target revealed important interactions between active compounds and amino acids, and several new potential inhibitors with higher activity predicted were designed basis on our analyses and supported by the simulation of molecular docking. Meanwhile, the OSIRIS Property Explorer was introduced to help select more satisfactory compounds. The satisfactory results from this study may lay a reliable theoretical base for drug development of hepatitis C virus NS5B polymerase inhibitors.

  3. Inhibitory mode of 1,5-diarylpyrazole derivatives against cyclooxygenase-2 and cyclooxygenase-1: molecular docking and 3D QSAR analyses.

    PubMed

    Liu, Hong; Huang, Xiaoqin; Shen, Jianhua; Luo, Xiaomin; Li, Minghui; Xiong, Bing; Chen, Gang; Shen, Jingkang; Yang, Yimin; Jiang, Hualiang; Chen, Kaixian

    2002-10-24

    The Lamarckian genetic algorithm of AutoDock 3.0 has been employed to dock 40 1,5-diarylpyrazole class compounds into the active sites of cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1). The binding models were demonstrated in the aspects of inhibitor's conformation, subsite interaction, and hydrogen bonding. The data of geometrical parameters and RMSD values compared with the known inhibitor, SC-558 (43), show that these inhibitors interact respectively with COX-2 and COX-1 in a very similar way. The r(2) values of 0.648 for COX-2 and 0.752 for COX-1 indicate that the calculated binding free energies correlate well with the inhibitory activities. The structural and energetic differences in inhibitory potencies of 1,5-diarylpyrazoles were reasonably explored, and the COX-2/COX-1 selectivity was demonstrated by the three-dimensional (3D) interaction models of inhibitors complexing with these two enzymes. Using the binding conformations of 1,5-diarylpyrazoles, consistent and highly predictive 3D quantitative structure-activity relationship (QSAR) models were developed by performing comparative molecular field analyses (CoMFA) and comparative molecular similarity analyses (CoMSIA). The q(2) values are 0.635 and 0.641 for CoMFA and CoMSIA models, respectively. The predictive ability of these models was validated by SC-558 (43) and a set of 10 other compounds that were not included in the training set. Mapping these models back to the topology of the active site of COX-2 leads to a better understanding of vital diarylpyrazole compounds and COX-2 interactions. Structure-based investigations and the final 3D QSAR results provided possible guidelines and accurate activity predictions for novel inhibitor design.

  4. 3D-QSAR studies on unsaturated 4-azasteroids as human 5alpha-reductase inhibitors: a self organizing molecular field analysis approach.

    PubMed

    Aggarwal, Saurabh; Thareja, Suresh; Bhardwaj, T R; Kumar, Manoj

    2010-02-01

    Azasteroids have been reported as inhibitors of human 5alpha-reductase enzyme. These were designed by substitution of one carbon atom of steroidal A ring by heteroatom nitrogen. Due to lack of information on the crystal structure of human 5alpha-reductase, 3D-QSAR study has been performed on a series of unsaturated 4-azasteroids using Self Organizing Molecular Field Analysis (SOMFA) for rationalizing the molecular properties and human 5alpha-reductase inhibitory activities. The statistical results having good cross-validated r(2)(cv) (0.783), non cross-validated r(2) (0.806) and F-test value (87.282), showed satisfied predictive ability. Analysis of SOMFA models through electrostatic and shape grids provide useful information for the design and optimization of new steroidal human 5alpha-reductase inhibitors.

  5. Molecular thermodynamics of trifluoroethanol-induced helix formation: analysis of the solvation structure and free energy by the 3D-RISM theory.

    PubMed

    Imai, Takashi; Kovalenko, Andriy; Hirata, Fumio; Kidera, Akinori

    2009-06-01

    It has been shown that trifluoroethanol (TFE) induces helical structure in peptides and proteins. The molecular mechanism is, however, still not completely elucidated. In this study, the TFE effects on the solvation structure and on the free energy change associated with the helix-coil transition of a polypeptide are analyzed by using the three-dimensional reference interaction site model (3D-RISM) molecular theory of solvation. The theoretical result shows that TFE preferentially solvates at low concentrations around 30 vol% both for the helix and coil structures. However, the characteristic preferential solvation is not as significant in the TFE-induced helix stabilization as generally considered. It is also found that the overall energy contributes to the free energy difference more substantially than the solvation entropy.

  6. Combined 3D-QSAR modeling and molecular docking studies on pyrrole-indolin-2-ones as Aurora A kinase inhibitors.

    PubMed

    Ai, Yong; Wang, Shao-Teng; Sun, Ping-Hua; Song, Fa-Jun

    2011-01-01

    Aurora kinases have emerged as attractive targets for the design of anticancer drugs. 3D-QSAR (comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)) and Surflex-docking studies were performed on a series of pyrrole-indoline-2-ones as Aurora A inhibitors. The CoMFA and CoMSIA models using 25 inhibitors in the training set gave r(2) (cv) values of 0.726 and 0.566, and r(2) values of 0.972 and 0.984, respectively. The adapted alignment method with the suitable parameters resulted in reliable models. The contour maps produced by the CoMFA and CoMSIA models were employed to rationalize the key structural requirements responsible for the activity. Surflex-docking studies revealed that the sulfo group, secondary amine group on indolin-2-one, and carbonyl of 6,7-dihydro-1H-indol-4(5H)-one groups were significant for binding to the receptor, and some essential features were also identified. Based on the 3D-QSAR and docking results, a set of new molecules with high predicted activities were designed.

  7. Identification of the Structural Features of Guanine Derivatives as MGMT Inhibitors Using 3D-QSAR Modeling Combined with Molecular Docking.

    PubMed

    Sun, Guohui; Fan, Tengjiao; Zhang, Na; Ren, Ting; Zhao, Lijiao; Zhong, Rugang

    2016-06-23

    DNA repair enzyme O⁶-methylguanine-DNA methyltransferase (MGMT), which plays an important role in inducing drug resistance against alkylating agents that modify the O⁶ position of guanine in DNA, is an attractive target for anti-tumor chemotherapy. A series of MGMT inhibitors have been synthesized over the past decades to improve the chemotherapeutic effects of O⁶-alkylating agents. In the present study, we performed a three-dimensional quantitative structure activity relationship (3D-QSAR) study on 97 guanine derivatives as MGMT inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. Three different alignment methods (ligand-based, DFT optimization-based and docking-based alignment) were employed to develop reliable 3D-QSAR models. Statistical parameters derived from the models using the above three alignment methods showed that the ligand-based CoMFA (Qcv² = 0.672 and Rncv² = 0.997) and CoMSIA (Qcv² = 0.703 and Rncv² = 0.946) models were better than the other two alignment methods-based CoMFA and CoMSIA models. The two ligand-based models were further confirmed by an external test-set validation and a Y-randomization examination. The ligand-based CoMFA model (Qext² = 0.691, Rpred² = 0.738 and slope k = 0.91) was observed with acceptable external test-set validation values rather than the CoMSIA model (Qext² = 0.307, Rpred² = 0.4 and slope k = 0.719). Docking studies were carried out to predict the binding modes of the inhibitors with MGMT. The results indicated that the obtained binding interactions were consistent with the 3D contour maps. Overall, the combined results of the 3D-QSAR and the docking obtained in this study provide an insight into the understanding of the interactions between guanine derivatives and MGMT protein, which will assist in designing novel MGMT inhibitors with desired activity.

  8. Perception-based shape retrieval for 3D building models

    NASA Astrophysics Data System (ADS)

    Zhang, Man; Zhang, Liqiang; Takis Mathiopoulos, P.; Ding, Yusi; Wang, Hao

    2013-01-01

    With the help of 3D search engines, a large number of 3D building models can be retrieved freely online. A serious disadvantage of most rotation-insensitive shape descriptors is their inability to distinguish between two 3D building models which are different at their main axes, but appear similar when one of them is rotated. To resolve this problem, we present a novel upright-based normalization method which not only correctly rotates such building models, but also greatly simplifies and accelerates the abstraction and the matching of building models' shape descriptors. Moreover, the abundance of architectural styles significantly hinders the effective shape retrieval of building models. Our research has shown that buildings with different designs are not well distinguished by the widely recognized shape descriptors for general 3D models. Motivated by this observation and to further improve the shape retrieval quality, a new building matching method is introduced and analyzed based on concepts found in the field of perception theory and the well-known Light Field descriptor. The resulting normalized building models are first classified using the qualitative shape descriptors of Shell and Unevenness which outline integral geometrical and topological information. These models are then put in on orderly fashion with the help of an improved quantitative shape descriptor which we will term as Horizontal Light Field Descriptor, since it assembles detailed shape characteristics. To accurately evaluate the proposed methodology, an enlarged building shape database which extends previous well-known shape benchmarks was implemented as well as a model retrieval system supporting inputs from 2D sketches and 3D models. Various experimental performance evaluation results have shown that, as compared to previous methods, retrievals employing the proposed matching methodology are faster and more consistent with human recognition of spatial objects. In addition these performance

  9. Interplay between spin-density wave and 3 d local moments with random exchange in a molecular conductor

    NASA Astrophysics Data System (ADS)

    Kawaguchi, Genta; Maesato, Mitsuhiko; Komatsu, Tokutaro; Imakubo, Tatsuro; Kitagawa, Hiroshi

    2016-02-01

    We present the results of high-pressure transport measurements on the anion-mixed molecular conductors (DIETSe)2M Br2Cl2 [DIETSe = diiodo(ethylenedithio)tetraselenafulvalene; M =Fe , Ga]. They undergo a metal-insulator (M-I) transition below 9 K at ambient pressure, which is suppressed by applying pressure, indicating a spin-density-wave (SDW) transition caused by a nesting instability of the quasi-one-dimensional (Q1D) Fermi surface, as observed in the parent compounds (DIETSe)2M Cl4 (M =Fe , Ga). In the metallic state, the existence of the Q1D Fermi surface is confirmed by observing the Lebed resonance. The critical pressures of the SDW, Pc, of the M Br2Cl2 (M =Fe , Ga) salts are significantly lower than those of the the M Cl4 (M = Fe, Ga) salts, suggesting chemical pressure effects. Above Pc, field-induced SDW transitions appear, as evidenced by kink structures in the magnetoresistance (MR) in both salts. The FeBr2Cl2 salt also shows antiferromagnetic (AF) ordering of d spins at 4 K, below which significant spin-charge coupling is observed. A large positive MR change up to 150% appears above the spin-flop field at high pressure. At low pressure, in particular below Pc, a dip or kink structure appears in MR at the spin-flop field, which shows unconventionally large hysteresis at low temperature (T <1 K). The hysteresis region clearly decreases with increasing pressure towards Pc, strongly indicating that the coexisting SDW plays an important role in the enhancement of magnetic hysteresis besides the random exchange interaction.

  10. Not that long time ago in the nearest galaxy: 3D slice of molecular gas revealed by a 110 yr old flare of Sgr A*

    NASA Astrophysics Data System (ADS)

    Churazov, E.; Khabibullin, I.; Sunyaev, R.; Ponti, G.

    2017-02-01

    A powerful outburst of X-ray radiation from the supermassive black hole Sgr A* at the centre of the Milky Way is believed to be responsible for the illumination of molecular clouds in the central ˜100 pc of the Galaxy (Sunyaev, Markevitch & Pavlinsky; Koyama et al.). The reflected/reprocessed radiation comes to us with a delay corresponding to the light propagation time that depends on the 3D position of molecular clouds with respect to Sgr A*. We suggest a novel way of determining the age of the outburst and positions of the clouds by studying characteristic imprints left by the outburst in the spatial and time variations of the reflected emission. We estimated the age of the outburst that illuminates the Sgr A molecular complex to be ˜110 yr. This estimate implies that we see the gas located ˜10 pc further away from us than Sgr A*. If the Sgr B2 complex is also illuminated by the same outburst, then it is located ˜130 pc closer than our Galactic Center. The outburst was short (less than a few years) and the total amount of emitted energy in X-rays is ˜10^{48}ρ _3^{-1} erg, where ρ3 is the mean hydrogen density of the cloud complex in units of 103 cm-3. Energetically, such fluence can be provided by a partial tidal disruption event or even by a capture of a planet. Further progress in more accurate positioning and timing of the outburst should be possible with future X-ray polarimetric observations and long-term systematic observations with Chandra and XMM-Newton. A few hundred years long X-ray observations would provide a detailed 3D map of the gas density distribution in the central ˜100 pc region.

  11. Molecular dynamics studies of side chain effect on the beta-1,3-D-glucan triple helix in aqueous solution.

    PubMed

    Okobira, Tadashi; Miyoshi, Kentaro; Uezu, Kazuya; Sakurai, Kazuo; Shinkai, Seiji

    2008-03-01

    beta-1,3-D-glucans have been isolated from fungi as right-handed 6(1) triple helices. They are categorized by the side chains bound to the main triple helix through beta-(1-->6)-D-glycosyl linkage. Indeed, since a glucose-based side chain is water soluble, the presence and frequency of glucose-based side chains give rise to significant variation in the physical properties of the glucan family. Curdlan has no side chains and self-assembles to form an water-insoluble triple helical structure, while schizophyllan, which has a 1,6-D-glucose side chain on every third glucose unit along the main chain, is completely water soluble. A thermal fluctuation in the optical rotatory dispersion is observed for the side chain, indicating probable co-operative interaction between the side chains and water molecules. This paper documents molecular dynamics simulations in aqueous solution for three models of the beta-1,3-D-glucan series: curdlan (no side chain), schizophyllan (a beta-(1-->6)-D-glycosyl side-chain at every third position), and a hypothetical triple helix with a side chain at every sixth main-chain glucose unit. A decrease was observed in the helical pitch as the population of the side chain increased. Two types of hydrogen bonding via water molecules, the side chain/main chain and the side chain/side chain hydrogen bonding, play an important role in determination of the triple helix conformation. The formation of a one-dimensional cavity of diameter about 3.5 A was observed in the schizophyllan triple helix, while curdlan showed no such cavity. The side chain/side chain hydrogen bonding in schizophyllan and the hypothetical beta-1,3-D-glucan triple helix could cause the tilt of the main-chain glucose residues to the helix.

  12. Europeana and 3D

    NASA Astrophysics Data System (ADS)

    Pletinckx, D.

    2011-09-01

    The current 3D hype creates a lot of interest in 3D. People go to 3D movies, but are we ready to use 3D in our homes, in our offices, in our communication? Are we ready to deliver real 3D to a general public and use interactive 3D in a meaningful way to enjoy, learn, communicate? The CARARE project is realising this for the moment in the domain of monuments and archaeology, so that real 3D of archaeological sites and European monuments will be available to the general public by 2012. There are several aspects to this endeavour. First of all is the technical aspect of flawlessly delivering 3D content over all platforms and operating systems, without installing software. We have currently a working solution in PDF, but HTML5 will probably be the future. Secondly, there is still little knowledge on how to create 3D learning objects, 3D tourist information or 3D scholarly communication. We are still in a prototype phase when it comes to integrate 3D objects in physical or virtual museums. Nevertheless, Europeana has a tremendous potential as a multi-facetted virtual museum. Finally, 3D has a large potential to act as a hub of information, linking to related 2D imagery, texts, video, sound. We describe how to create such rich, explorable 3D objects that can be used intuitively by the generic Europeana user and what metadata is needed to support the semantic linking.

  13. Design, synthesis and molecular modeling of novel pyrido[2,3-d]pyrimidine analogs as antifolates: Application of Buchwald-Hartwig aminations of heterocycles

    PubMed Central

    Gangjee, Aleem; Namjoshi, Ojas A.; Raghavan, Sudhir; Queener, Sherry F.; Kisliuk, Roy L.; Cody, Vivian

    2013-01-01

    Opportunistic infections caused by Pneumocystis jirovecii (P. jirovecii, pj), Toxoplasma gondii (T. gondii, tg) and Mycobacterium avium (M. avium, ma) are the principal causes of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). The absence of any animal models for human Pneumocystis jirovecii pneumonia and the lack of crystal structures of pjDHFR and tgDHFR make the design of inhibitors challenging. A novel series of pyrido[2,3-d]pyrimidines as selective and potent DHFR inhibitors against these opportunistic infections are presented. Buchwald-Hartwig coupling reaction of substituted anilines with pivaloyl protected 2,4-diamino-6-bromo-pyrido[2,3-d]pyrimidine was successfully explored to synthesize these analogs. Compound 26 was the most selective inhibitor with excellent potency against pjDHFR. Molecular modeling studies with a pjDHFR homology model explained the potency and selectivity of 26. Structural data are also reported for 26 with pcDHFR and 16 and 22 with variants of pcDHFR. PMID:23627352

  14. An in vivo validation of the application of acoustic radiation force to enhance the diagnostic utility of molecular imaging using 3-d ultrasound.

    PubMed

    Gessner, Ryan C; Streeter, Jason E; Kothadia, Roshni; Feingold, Steven; Dayton, Paul A

    2012-04-01

    For more than a decade, the application of acoustic radiation force (ARF) has been proposed as a mechanism to increase ultrasonic molecular imaging (MI) sensitivity in vivo. Presented herein is the first noninvasive in vivo validation of ARF-enhanced MI with an unmodified clinical system. First, an in vitro optical-acoustical setup was used to optimize system parameters and ensure sufficient microbubble translation when exposed to ARF. 3-D ARF-enhanced MI was then performed on 7 rat fibrosarcoma tumors using microbubbles targeted to α(v)β₃ and nontargeted microbubbles. Low-amplitude (<25 kPa) 3-D ARF pulse sequences were tested and compared with passive targeting studies in the same animal. Our results demonstrate that a 78% increase in image intensity from targeted microbubbles can be achieved when using ARF relative to the passive targeting studies. Furthermore, ARF did not significantly increase image contrast when applied to nontargeted agents, suggesting that ARF did not increase nonspecific adhesion.

  15. Topological and quantum molecular descriptors as effective tools for analyzing cytotoxic activity achieved by a series of (diselanediyldibenzene-4,1-diylnide)biscarbamate derivatives.

    PubMed

    Font, María; Plano, Daniel; Sanmartín, Carmen; Palop, Juan Antonio

    2017-05-01

    A molecular modeling study has been carried out on a previously reported series of (diselanediyldibenzene-4,1-diylnide)biscarbamate derivatives that show cytotoxic and antiproliferative in vitro activity against MCF-7 human cell line; radical scavenging properties were also confirmed when these compounds were tested for their ability to scavenge DPPH and ABTS radicals. The data obtained allowed us to classify the compounds into two different groups: (a) aliphatic carbamates for which the activity could be related with a first nucleophilic attack (mediated by H2O, for example) on the selenium atoms of the central scaffold, followed by the release of the alkyl N-(4-selanylphenyl) and N-(4-selenenophenyl)carbamate moieties. Then, a second nucleophilic attack on the carbamate moiety, to yield 4-aminobenzeneselenol and 4-selenenoaniline respectively, which can ultimately be responsible for the activity of the compounds; (b) aromatic carbamates, for which we propose a preferred nucleophilic attack on the carbamate moiety, yielding 4-[(4-aminophenyl)diselanyl]aniline, the common structural fragment for this series, for which we have previously demonstrated its cytotoxic profile. Then, selenium atoms of the central fragment may later undergo a new nucleophilic attack, to yield 4-selenenoaniline and 4-aminobenzeneselenol. The phenolic moieties released in this process may also have a synergistic cytotoxic and redox activity. The data that support this connection include the conformational behavior and the molecular topography of the derivatives which can influence the accessibility of the hydrolysis points, and some quantum descriptors (bond order, atomic charges, total valences, ionization potential, electron affinity, HOMO 0 and LUMO 0 location, etc.) that have been related to the biological activity of the compounds.

  16. Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7

    PubMed Central

    Ismail, Hanafy M.; Barton, Victoria; Phanchana, Matthew; Charoensutthivarakul, Sitthivut; Wong, Michael H. L.; Hemingway, Janet; Biagini, Giancarlo A.; O’Neill, Paul M.; Ward, Stephen A.

    2016-01-01

    The artemisinin (ART)-based antimalarials have contributed significantly to reducing global malaria deaths over the past decade, but we still do not know how they kill parasites. To gain greater insight into the potential mechanisms of ART drug action, we developed a suite of ART activity-based protein profiling probes to identify parasite protein drug targets in situ. Probes were designed to retain biological activity and alkylate the molecular target(s) of Plasmodium falciparum 3D7 parasites in situ. Proteins tagged with the ART probe can then be isolated using click chemistry before identification by liquid chromatography–MS/MS. Using these probes, we define an ART proteome that shows alkylated targets in the glycolytic, hemoglobin degradation, antioxidant defense, and protein synthesis pathways, processes essential for parasite survival. This work reveals the pleiotropic nature of the biological functions targeted by this important class of antimalarial drugs. PMID:26858419

  17. Deep Nonlinear Metric Learning for 3-D Shape Retrieval.

    PubMed

    Xie, Jin; Dai, Guoxian; Zhu, Fan; Shao, Ling; Fang, Yi

    2016-12-28

    Effective 3-D shape retrieval is an important problem in 3-D shape analysis. Recently, feature learning-based shape retrieval methods have been widely studied, where the distance metrics between 3-D shape descriptors are usually hand-crafted. In this paper, motivated by the fact that deep neural network has the good ability to model nonlinearity, we propose to learn an effective nonlinear distance metric between 3-D shape descriptors for retrieval. First, the locality-constrained linear coding method is employed to encode each vertex on the shape and the encoding coefficient histogram is formed as the global 3-D shape descriptor to represent the shape. Then, a novel deep metric network is proposed to learn a nonlinear transformation to map the 3-D shape descriptors to a nonlinear feature space. The proposed deep metric network minimizes a discriminative loss function that can enforce the similarity between a pair of samples from the same class to be small and the similarity between a pair of samples from different classes to be large. Finally, the distance between the outputs of the metric network is used as the similarity for shape retrieval. The proposed method is evaluated on the McGill, SHREC'10 ShapeGoogle, and SHREC'14 Human shape datasets. Experimental results on the three datasets validate the effectiveness of the proposed method.

  18. TOPS-MODE versus DRAGON descriptors to predict permeability coefficients through low-density polyethylene

    NASA Astrophysics Data System (ADS)

    González, Maykel Pérez; Helguera, Aliuska Morales

    2003-10-01

    The TOPological Sub-Structural MOlecular DEsign (TOPS-MODE) approach has been applied to the study of the permeability coefficient of various compounds through low-density polyethylene at 0 °C. A model able to describe more than 92% of the variance in the experimental permeability of 38 organic compounds was developed with the use of the mentioned approach. In contrast, none of eight different approaches, including the use of constitutional, topological, BCUT, 2D autocorrelations, geometrical, RDF, 3D Morse, and GETAWAY descriptors was able to explain more than 75% of the variance in the mentioned property with the same number of descriptors. In addition, the TOPS-MODE approach permitted to find the contribution of different fragments to the permeability coefficients, giving to the model a straightforward structural interpretability.

  19. 3d-3d correspondence revisited

    DOE PAGES

    Chung, Hee -Joong; Dimofte, Tudor; Gukov, Sergei; ...

    2016-04-21

    In fivebrane compactifications on 3-manifolds, we point out the importance of all flat connections in the proper definition of the effective 3d N = 2 theory. The Lagrangians of some theories with the desired properties can be constructed with the help of homological knot invariants that categorify colored Jones polynomials. Higgsing the full 3d theories constructed this way recovers theories found previously by Dimofte-Gaiotto-Gukov. As a result, we also consider the cutting and gluing of 3-manifolds along smooth boundaries and the role played by all flat connections in this operation.

  20. Combined 3D-QSAR, molecular docking, molecular dynamics simulation, and binding free energy calculation studies on the 5-hydroxy-2H-pyridazin-3-one derivatives as HCV NS5B polymerase inhibitors.

    PubMed

    Yu, Haijing; Fang, Yu; Lu, Xia; Liu, Yongjuan; Zhang, Huabei

    2014-01-01

    The NS5B RNA-dependent RNA polymerase (RdRP) is a promising therapeutic target for developing novel anti-hepatitis C virus (HCV) drugs. In this work, a combined molecular modeling study was performed on a series of 193 5-hydroxy-2H-pyridazin-3-one derivatives as inhibitors of HCV NS5B Polymerase. The best 3D-QSAR models, including CoMFA and CoMSIA, are based on receptor (or docking). Furthermore, a 40-ns molecular dynamics (MD) simulation and binding free energy calculations using docked structures of NS5B with ten compounds, which have diverse structures and pIC50 values, were employed to determine the detailed binding process and to compare the binding modes of the inhibitors with different activities. On one side, the stability and rationality of molecular docking and 3D-QSAR results were validated by MD simulation. The binding free energies calculated by the MM-PBSA method gave a good correlation with the experimental biological activity. On the other side, by analyzing some differences between the molecular docking and the MD simulation results, we can find that the MD simulation could also remedy the defects of molecular docking. The analyses of the combined molecular modeling results have identified that Tyr448, Ser556, and Asp318 are the key amino acid residues in the NS5B binding pocket. The results from this study can provide some insights into the development of novel potent NS5B inhibitors.

  1. Toll-like receptor 22 in Labeo rohita: molecular cloning, characterization, 3D modeling, and expression analysis following ligands stimulation and bacterial infection.

    PubMed

    Samanta, Mrinal; Swain, Banikalyan; Basu, Madhubanti; Mahapatra, Girishbala; Sahoo, Bikash R; Paichha, Mahismita; Lenka, Saswati S; Jayasankar, Pallipuram

    2014-09-01

    Toll-like receptors (TLRs) are a class of innate immune receptors that sense pathogens or their molecular signatures and activate signaling cascades to induce a quick and non-specific immune response in the host. Among various types of TLRs, TLR22 is exclusively present in teleosts and amphibians and is expected to play the distinctive role in innate immunity. This report describes molecular cloning, three-dimensional (3D) modeling, and expression analysis of TLR22 in rohu (Labeo rohita), the most commercially important freshwater fish species in the Indian subcontinent. The open reading frame (ORF) of rohu TLR22 (LrTLR22) comprised of 2,838 nucleotides (nt), encoding 946 amino acid (aa) residues with the molecular mass of ∼ 107.6 kDa. The secondary structure of deduced LrTLR22 exhibited the presence of signal peptide (1-22 aa), 18 leucine-rich repeat (LRR) regions (79-736 aa), and TIR domain (792-935 aa). The 3D model of LrTLR22-LRR regions together elucidated the horse-shoe-shaped structure having parallel β-strands at the concave surface and few α-helices at the convex surface. The TIR domain structure revealed alternate presence of five α-helices and β-sheets. Phylogenetically, LrTLR22 was closely related to common carp and exhibited significant similarity (92.2 %) and identity (86.1 %) in their amino acids. In rohu, TLR22 was constitutively expressed in all embryonic developmental stages, and tissue-specific analysis illustrated its expression in all examined tissues, highest was in liver and lowest in brain. In vivo modulation of TLR22 gene expression was analyzed by quantitative real-time PCR (qRT-PCR) assay following stimulation with lipopolysaccharide (LPS), synthetic double stranded RNA (polyinosinic-polycytidylic acid), and bacterial (Aeromonas hydrophila) RNA. Among these ligands, bacterial RNA most significantly (p < 0.05) induced TLR22 gene expression in most of the tested tissues. In A. hydrophila infection, induction of TLR22 gene expression

  2. Analysis of local molecular motions of aromatic sidechains in proteins by 2D and 3D fast MAS NMR spectroscopy and quantum mechanical calculations.

    PubMed

    Paluch, Piotr; Pawlak, Tomasz; Jeziorna, Agata; Trébosc, Julien; Hou, Guangjin; Vega, Alexander J; Amoureux, Jean-Paul; Dracinsky, Martin; Polenova, Tatyana; Potrzebowski, Marek J

    2015-11-21

    We report a new multidimensional magic angle spinning NMR methodology, which provides an accurate and detailed probe of molecular motions occurring on timescales of nano- to microseconds, in sidechains of proteins. The approach is based on a 3D CPVC-RFDR correlation experiment recorded under fast MAS conditions (ν(R) = 62 kHz), where (13)C-(1)H CPVC dipolar lineshapes are recorded in a chemical shift resolved manner. The power of the technique is demonstrated in model tripeptide Tyr-(d)Ala-Phe and two nanocrystalline proteins, GB1 and LC8. We demonstrate that, through numerical simulations of dipolar lineshapes of aromatic sidechains, their detailed dynamic profile, i.e., the motional modes, is obtained. In GB1 and LC8 the results unequivocally indicate that a number of aromatic residues are dynamic, and using quantum mechanical calculations, we correlate the molecular motions of aromatic groups to their local environment in the crystal lattice. The approach presented here is general and can be readily extended to other biological systems.

  3. 3D-QSAR and molecular modeling studies on 2,3-dideoxy hexenopyranosid-4-uloses as anti-tubercular agents targeting alpha-mannosidase.

    PubMed

    Shah, Priyanka; Saquib, Mohammad; Sharma, Smriti; Husain, Irfan; Sharma, Sandeep K; Singh, Vinayak; Srivastava, Ranjana; Shaw, Arun K; Siddiqi, Mohammad Imran

    2015-04-01

    Ligand-based and structure-based methods were applied in combination to exploit the physicochemical properties of 2,3-dideoxy hex-2-enopyranosid-4-uloses against Mycobacterium tuberculosis H37Rv. Statistically valid 3D-QSAR models with good correlation and predictive power were obtained with CoMFA steric and electrostatic fields (r(2) = 0.797, q(2) = 0.589) and CoMSIA with combined steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (r(2) = 0.867, q(2) = 0.570) based on training set of 33 molecules with predictive r(2) of 0.808 and 0.890 for CoMFA and CoMSIA respectively. The results illustrate the requirement of optimal alkyl chain length at C-1 position and acceptor groups along hydroxy methyl substituent of C-6 to enhance the anti-tubercular activity of the 2,3-dideoxy hex-2-enopyranosid-4-uloses while any substitution at C-3 position exert diminishing effect on anti-tubercular activity of these enulosides. Further, homology modeling of M. tuberculosis alpha-mannosidase followed by molecular docking and molecular dynamics simulations on co-complexed models were performed to gain insight into the rationale for binding affinity of selected inhibitors with the target of interest. The comprehensive information obtained from this study will help to better understand the structural basis of biological activity of this class of molecules and guide further design of more potent analogues as anti-tubercular agents.

  4. 3D QSAR STUDIES ON A SERIES OF QUINAZOLINE DERRIVATIVES AS TYROSINE KINASE (EGFR) INHIBITOR: THE K-NEAREST NEIGHBOR MOLECULAR FIELD ANALYSIS APPROACH

    PubMed Central

    Noolvi, Malleshappa N.; Patel, Harun M.

    2010-01-01

    Epidermal growth factor receptor (EGFR) protein tyrosine kinases (PTKs) are known for its role in cancer. Quinazoline have been reported to be the molecules of interest, with potent anticancer activity and they act by binding to ATP site of protein kinases. ATP binding site of protein kinases provides an extensive opportunity to design newer analogs. With this background, we report an attempt to discern the structural and physicochemical requirements for inhibition of EGFR tyrosine kinase. The k-Nearest Neighbor Molecular Field Analysis (kNN-MFA), a three dimensional quantitative structure activity relationship (3D- QSAR) method has been used in the present case to study the correlation between the molecular properties and the tyrosine kinase (EGFR) inhibitory activities on a series of quinazoline derivatives. kNNMFA calculations for both electrostatic and steric field were carried out. The master grid maps derived from the best model has been used to display the contribution of electrostatic potential and steric field. The statistical results showed significant correlation coefficient r2 (q2) of 0.846, r2 for external test set (pred_r2) 0.8029, coefficient of correlation of predicted data set (pred_r2se) of 0.6658, degree of freedom 89 and k nearest neighbor of 2. Therefore, this study not only casts light on binding mechanism between EGFR and its inhibitors, but also provides hints for the design of new EGFR inhibitors with observable structural diversity PMID:24825983

  5. Reaction of 1Н,2Н,3Н,4Н-pyrido[4,3-d]pyrimidinium bromide derivatives with molecular iodine: Comparative structure and spectroscopic analysis

    NASA Astrophysics Data System (ADS)

    Chernov'yants, Margarita S.; Burykin, Igor V.; Kostrub, Vladimir V.; Tsupak, Evgeny B.; Starikova, Zoya A.; Kirsanova, Julia A.

    2012-02-01

    New salts C27H22N3O2BrI2 (1) and C27H19N3O2Br4I2·2CHCl3·2H2O (2) were synthesized by the iodination of derivatives of 1,3-dimethyl-2,4-dioxo-5,6,7-R-1Н,2Н,3Н,4Н-pyrido[4,3-d]pyrimidinium bromide (R = phenyl (1a), p-bromphenyl (2a)) with an equimolar amount of iodine. The positive values of enthalpy (ΔH) and entropy (ΔS) indicate that the complexation of organic bromide and iodine molecule in chloroform solution is mainly entropically driven. The molecular and crystal structures (1) and (2) are studied by X-ray diffraction analysis. The structure of diiodinebromide 1 is composed of separate almost liner BrI2- and 1,3-dimethyl-2,4-dioxo-5,6,7-thriphenyl-1Н,2Н,3Н,4Н-pyrido[4,3-d]pyrimidinium cation. The crystal structure 2 is built up of alternate layers of (CHNOBr3+)(I3-) (A) and (Br2I-)(СHСl3) (B), connected to each other by hydrogen bonds Br(BrI)⋯H(CHNOBr3+). The formation of the ions I3- and Br2I- occurs via the disproportionation of I2Br- under the action of solvent on C27H19N3O2Br4I2·2CHCl3·2H2O (2) crystallization.

  6. 3D and Education

    NASA Astrophysics Data System (ADS)

    Meulien Ohlmann, Odile

    2013-02-01

    Today the industry offers a chain of 3D products. Learning to "read" and to "create in 3D" becomes an issue of education of primary importance. 25 years professional experience in France, the United States and Germany, Odile Meulien set up a personal method of initiation to 3D creation that entails the spatial/temporal experience of the holographic visual. She will present some different tools and techniques used for this learning, their advantages and disadvantages, programs and issues of educational policies, constraints and expectations related to the development of new techniques for 3D imaging. Although the creation of display holograms is very much reduced compared to the creation of the 90ies, the holographic concept is spreading in all scientific, social, and artistic activities of our present time. She will also raise many questions: What means 3D? Is it communication? Is it perception? How the seeing and none seeing is interferes? What else has to be taken in consideration to communicate in 3D? How to handle the non visible relations of moving objects with subjects? Does this transform our model of exchange with others? What kind of interaction this has with our everyday life? Then come more practical questions: How to learn creating 3D visualization, to learn 3D grammar, 3D language, 3D thinking? What for? At what level? In which matter? for whom?

  7. Receptor-based 3D-QSAR in Drug Design: Methods and Applications in Kinase Studies.

    PubMed

    Fang, Cheng; Xiao, Zhiyan

    2016-01-01

    Receptor-based 3D-QSAR strategy represents a superior integration of structure-based drug design (SBDD) and three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis. It combines the accurate prediction of ligand poses by the SBDD approach with the good predictability and interpretability of statistical models derived from the 3D-QSAR approach. Extensive efforts have been devoted to the development of receptor-based 3D-QSAR methods and two alternative approaches have been exploited. One associates with computing the binding interactions between a receptor and a ligand to generate structure-based descriptors for QSAR analyses. The other concerns the application of various docking protocols to generate optimal ligand poses so as to provide reliable molecular alignments for the conventional 3D-QSAR operations. This review highlights new concepts and methodologies recently developed in the field of receptorbased 3D-QSAR, and in particular, covers its application in kinase studies.

  8. Discrete Derivatives for Atom-Pairs as a Novel Graph-Theoretical Invariant for Generating New Molecular Descriptors: Orthogonality, Interpretation and QSARs/QSPRs on Benchmark Databases.

    PubMed

    Martínez-Santiago, Oscar; Millán-Cabrera, Reisel; Marrero-Ponce, Yovani; Barigye, Stephen J; Martínez-López, Yoan; Torrens, Francisco; Pérez-Giménez, Facundo

    2014-05-01

    This report presents a new mathematical method based on the concept of the derivative of a molecular graph (G) with respect to a given event (S) to codify chemical structure information. The derivate over each pair of atoms in the molecule is defined as ∂G/∂S(vi  , vj )=(fi -2fij +fj )/fij , where fi (or fj ) and fij are the individual frequency of atom i (or j) and the reciprocal frequency of the atoms i and j, respectively. These frequencies characterize the participation intensity of atom pairs in S. Here, the event space is composed of molecular sub-graphs which participate in the formation of the G skeleton that could be complete (representing all possible connected sub-graphs) or comprised of sub-graphs of certain orders or types or combinations of these. The atom level graph derivative index, Δi , is expressed as a linear combination of all atom pair derivatives that include the atomic nuclei i. Global [total or local (group or atom-type)] indices are obtained by applying the so called invariants over a vector of Δi values. The novel MDs are validated using a data set of 28 alkyl-alcohols and other benchmark data sets proposed by the International Academy of Mathematical Chemistry. Also, the boiling point for the alcohols, the adrenergic blocking activity of N,N-dimethyl-2-halo-phenethylamines and physicochemical properties of polychlorinated biphenyls and octanes are modeled. These models exhibit satisfactory predictive power compared with other 0-3D indices implemented successfully by other researchers. In addition, tendencies of the proposed indices are investigated using examples of various types of molecular structures, including chain-lengthening, branching, heteroatoms-content, and multiple bonds. On the other hand, the relation of atom-based derivative indices with (17) O NMR of a series of ethers and carbonyls reflects that the new MDs encode electronic, topological and steric information. Linear independence between the graph derivative

  9. 3D-QSAR, molecular dynamics simulations and molecular docking studies of benzoxazepine moiety as mTOR inhibitor for the treatment of lung cancer.

    PubMed

    Chaube, Udit; Chhatbar, Dhara; Bhatt, Hardik

    2016-02-01

    According to WHO statistics, lung cancer is one of the leading causes of death among all other types of cancer. Many genes get mutated in lung cancer but involvement of EGFR and KRAS are more common. Unavailability of drugs or resistance to the available drugs is the major problem in the treatment of lung cancer. In the present research, mTOR was selected as an alternative target for the treatment of lung cancer which involves PI3K/AKT/mTOR pathway. 28 synthetic mTOR inhibitors were selected from the literature. Ligand based approach (CoMFA and CoMSIA) and structure based approach (molecular dynamics simulations assisted molecular docking study) were applied for the identification of important features of benzoxazepine moiety, responsible for mTOR inhibition. Three different alignments were tried to obtain best QSAR model, of which, distil was found to be the best method, as it gave good statistical results. In CoMFA, Leave One Out (LOO) cross validated coefficients (q(2)), conventional coefficient (r(2)) and predicted correlation coefficient (r(2)pred) values were found to be 0.615, 0.990 and 0.930, respectively. Similarly in CoMSIA, q(2), r(2)ncv and r(2)pred values were found to be 0.748, 0.986 and 0.933, respectively. Molecular dynamics and simulations study revealed that B-chain of mTOR protein was stable at and above 500 FS with respect to temperature (at and above 298 K), Potential energy (at and above 7669.72 kJ/mol) and kinetic energy (at and above 4009.77 kJ/mol). Molecular docking study was performed on simulated protein of mTOR which helped to correlate interactions of amino acids surrounded to the ligand with contour maps generated by QSAR method. Important features of benzoxazepine were identified by contour maps and molecular docking study which would be useful to design novel molecules as mTOR inhibitors for the treatment of lung cancer.

  10. Novel electrochemical sensing platform based on a molecularly imprinted polymer decorated 3D nanoporous nickel skeleton for ultrasensitive and selective determination of metronidazole.

    PubMed

    Li, Yingchun; Liu, Yuan; Yang, Yang; Yu, Feng; Liu, Jie; Song, Han; Liu, Jiang; Tang, Hui; Ye, Bang-Ce; Sun, Zhipeng

    2015-07-22

    A novel electrochemical sensor has been developed by using a composite element of three-dimensional (3D) nanoporous nickel (NPNi) and molecularly imprinted polymer (MIP). NPNi is introduced in order to enhance the electron-transport ability and surface area of the sensor, while the electrosynthesized MIP layer affords simultaneous identification and quantification of the target molecule by employing Fe(CN)6(3-/4-) as the probe to indicate the current intensity. The morphology of the hybrid film was observed by scanning electron microscopy, and the properties of the sensor were examined by cyclic voltammetry and electrochemical impedance spectroscopy. By using metronidazole (MNZ) as a model analyte, the sensor based on the MIP/NPNi hybrid exhibits great features such as a remarkably low detection limit of 2 × 10(-14) M (S/N = 3), superb selectivity in discriminating MNZ from its structural analogues, and good antiinterference ability toward several coexisting substances. Moreover, the proposed method also demonstrates excellent repeatability and stability, with relative standard deviations of less than 1.12% and 1.4%, respectively. Analysis of MNZ in pharmaceutical dosage form and fish tissue is successfully carried out without assistance of complicated pretreatment. The MIP/NPNi composite presented here with admirable merits makes it a promising candidate for developing electrochemical sensor devices and plays a role in widespread fields.

  11. Student Descriptor Scale Manual.

    ERIC Educational Resources Information Center

    Goetz, Lori; And Others

    The Student Descriptor Scale (SDS) was developed as a validation measure to determine whether students described and counted by states as "severely handicapped" were, indeed, students with severe disabilities. The SDS addresses nine characteristics: intellectual disability, health impairment, need for toileting assistance, upper torso motor…

  12. 3D in vivo imaging of GFP-expressing T-cells in mice with non-contact fluorescence molecular tomography

    NASA Astrophysics Data System (ADS)

    Garofalakis, Anikitos; Meyer, Heiko; Zacharakis, Giannis; Mamalaki, Clio; Papamatheakis, Joseph; Ntziachristos, Vasilis; Economou, Eleftherios N.; Ripoll, J.

    2006-03-01

    Optical tomography has been proposed as a promising technique for probing deep in tissue with many medical applications. Recently, the adaptation of fluorescent probes by the radiologists, gave rise to a new imaging tool in the area of molecular imaging. Optical tomography can, provide three-dimensional images of fluorescent concentrations inside living systems of sizes in the order of many cm. Our optical tomographer was based on a technique which is called Fluorescence Molecular Tomography (FMT) and can quantify fluorescent signals in mice. The imaging procedure is performed in a non-contact geometry so that living subjects of arbitrary shapes can be imaged with no fibers attached to them. We have developed a way to reconstruct the 3D surface of the subject and we use theoretical models to account for the propagation of the emerging signal in the free space. The system consists of a rotating sample holder and a CCD camera in combination with a laser-scanning device. An Argon-ion laser is used as the source and different filters are used for the detection of various fluorophores or fluorescing proteins. So far, we have observed of the distribution of GFP expressing T-lymphocytes in-vivo for the study of the function of the immune system in a murine model. Then we investigated the performance of the FMT setup to quantify the different amounts of migrated cells in the different organs by comparing our results with the FACS measurements. Further experiments included the measurement of the variations of the T cell's concentration in-vivo, over time.

  13. Molecular cloning, expression pattern, and 3D structural prediction of the cold inducible RNA-binding protein (CIRP) in Japanese flounder ( Paralichthys olivaceus)

    NASA Astrophysics Data System (ADS)

    Yang, Xiao; Gao, Jinning; Ma, Liman; Li, Zan; Wang, Wenji; Wang, Zhongkai; Yu, Haiyang; Qi, Jie; Wang, Xubo; Wang, Zhigang; Zhang, Quanqi

    2015-02-01

    Cold-inducible RNA-binding protein (CIRP) is a kind of RNA binding proteins that plays important roles in many physiological processes. The CIRP has been widely studied in mammals and amphibians since it was first cloned from mammals. On the contrary, there are little reports in teleosts. In this study, the Po CIRP gene of the Japanese flounder was cloned and sequenced. The genomic sequence consists of seven exons and six introns. The putative PoCIRP protein of flounder was 198 amino acid residues long containing the RNA recognition motif (RRM). Phylogenetic analysis showed that the flounder PoCIRP is highly conserved with other teleost CIRPs. The 5' flanking sequence was cloned by genome walking and many transcription factor binding sites were identified. There is a CpGs region located in promoter and exon I region and the methylation state is low. Quantitative real-time PCR analysis uncovered that Po CIRP gene was widely expressed in adult tissues with the highest expression level in the ovary. The mRNA of the Po CIRP was maternally deposited and the expression level of the gene was regulated up during the gastrula and neurula stages. In order to gain the information how the protein interacts with mRNA, we performed the modeling of the 3D structure of the flounder PoCIRP. The results showed a cleft existing the surface of the molecular. Taken together, the results indicate that the CIRP is a multifunctional molecular in teleosts and the findings about the structure provide valuable information for understanding the basis of this protein's function.

  14. Macrophage podosomes go 3D.

    PubMed

    Van Goethem, Emeline; Guiet, Romain; Balor, Stéphanie; Charrière, Guillaume M; Poincloux, Renaud; Labrousse, Arnaud; Maridonneau-Parini, Isabelle; Le Cabec, Véronique

    2011-01-01

    Macrophage tissue infiltration is a critical step in the immune response against microorganisms and is also associated with disease progression in chronic inflammation and cancer. Macrophages are constitutively equipped with specialized structures called podosomes dedicated to extracellular matrix (ECM) degradation. We recently reported that these structures play a critical role in trans-matrix mesenchymal migration mode, a protease-dependent mechanism. Podosome molecular components and their ECM-degrading activity have been extensively studied in two dimensions (2D), but yet very little is known about their fate in three-dimensional (3D) environments. Therefore, localization of podosome markers and proteolytic activity were carefully examined in human macrophages performing mesenchymal migration. Using our gelled collagen I 3D matrix model to obligate human macrophages to perform mesenchymal migration, classical podosome markers including talin, paxillin, vinculin, gelsolin, cortactin were found to accumulate at the tip of F-actin-rich cell protrusions together with β1 integrin and CD44 but not β2 integrin. Macrophage proteolytic activity was observed at podosome-like protrusion sites using confocal fluorescence microscopy and electron microscopy. The formation of migration tunnels by macrophages inside the matrix was accomplished by degradation, engulfment and mechanic compaction of the matrix. In addition, videomicroscopy revealed that 3D F-actin-rich protrusions of migrating macrophages were as dynamic as their 2D counterparts. Overall, the specifications of 3D podosomes resembled those of 2D podosome rosettes rather than those of individual podosomes. This observation was further supported by the aspect of 3D podosomes in fibroblasts expressing Hck, a master regulator of podosome rosettes in macrophages. In conclusion, human macrophage podosomes go 3D and take the shape of spherical podosome rosettes when the cells perform mesenchymal migration. This work

  15. 3D Imaging.

    ERIC Educational Resources Information Center

    Hastings, S. K.

    2002-01-01

    Discusses 3 D imaging as it relates to digital representations in virtual library collections. Highlights include X-ray computed tomography (X-ray CT); the National Science Foundation (NSF) Digital Library Initiatives; output peripherals; image retrieval systems, including metadata; and applications of 3 D imaging for libraries and museums. (LRW)

  16. Modular Chemical Descriptor Language (MCDL): Stereochemical modules

    SciTech Connect

    Gakh, Andrei A; Burnett, Michael N; Trepalin, Sergei V.; Yarkov, Alexander V

    2011-01-01

    In our previous papers we introduced the Modular Chemical Descriptor Language (MCDL) for providing a linear representation of chemical information. A subsequent development was the MCDL Java Chemical Structure Editor which is capable of drawing chemical structures from linear representations and generating MCDL descriptors from structures. In this paper we present MCDL modules and accompanying software that incorporate unique representation of molecular stereochemistry based on Cahn-Ingold-Prelog and Fischer ideas in constructing stereoisomer descriptors. The paper also contains additional discussions regarding canonical representation of stereochemical isomers, and brief algorithm descriptions of the open source LINDES, Java applet, and Open Babel MCDL processing module software packages. Testing of the upgraded MCDL Java Chemical Structure Editor on compounds taken from several large and diverse chemical databases demonstrated satisfactory performance for storage and processing of stereochemical information in MCDL format.

  17. 3D Printed Bionic Nanodevices.

    PubMed

    Kong, Yong Lin; Gupta, Maneesh K; Johnson, Blake N; McAlpine, Michael C

    2016-06-01

    The ability to three-dimensionally interweave biological and functional materials could enable the creation of bionic devices possessing unique and compelling geometries, properties, and functionalities. Indeed, interfacing high performance active devices with biology could impact a variety of fields, including regenerative bioelectronic medicines, smart prosthetics, medical robotics, and human-machine interfaces. Biology, from the molecular scale of DNA and proteins, to the macroscopic scale of tissues and organs, is three-dimensional, often soft and stretchable, and temperature sensitive. This renders most biological platforms incompatible with the fabrication and materials processing methods that have been developed and optimized for functional electronics, which are typically planar, rigid and brittle. A number of strategies have been developed to overcome these dichotomies. One particularly novel approach is the use of extrusion-based multi-material 3D printing, which is an additive manufacturing technology that offers a freeform fabrication strategy. This approach addresses the dichotomies presented above by (1) using 3D printing and imaging for customized, hierarchical, and interwoven device architectures; (2) employing nanotechnology as an enabling route for introducing high performance materials, with the potential for exhibiting properties not found in the bulk; and (3) 3D printing a range of soft and nanoscale materials to enable the integration of a diverse palette of high quality functional nanomaterials with biology. Further, 3D printing is a multi-scale platform, allowing for the incorporation of functional nanoscale inks, the printing of microscale features, and ultimately the creation of macroscale devices. This blending of 3D printing, novel nanomaterial properties, and 'living' platforms may enable next-generation bionic systems. In this review, we highlight this synergistic integration of the unique properties of nanomaterials with the

  18. AE3D

    SciTech Connect

    Spong, Donald A

    2016-06-20

    AE3D solves for the shear Alfven eigenmodes and eigenfrequencies in a torodal magnetic fusion confinement device. The configuration can be either 2D (e.g. tokamak, reversed field pinch) or 3D (e.g. stellarator, helical reversed field pinch, tokamak with ripple). The equations solved are based on a reduced MHD model and sound wave coupling effects are not currently included.

  19. Stabilizing factors of the molecular structure in silicon-based peptidomimetics in gas-phase and water solution. Assessment of the correlation between different descriptors of hydrogen bond strength.

    PubMed

    Rodríguez Ortega, María Pilar Gema; Montejo, Manuel; López González, Juan Jesús

    2013-10-01

    The use of DFT (B3LYP and M06L) and ab initio (MP2) computational methods allowed us to perform a thorough conformational study of N-[dihydroxy (methyl)silyl]methylformamide (DHSF) and 3-[dihydroxy (methyl) silyl] propanamide (DHSP), that could be considered simplified models of the environment of the silanediol group in silicon gem-diols that have proven efficiency as protease inhibitors. We have found a total of 13 molecular conformations that represent minima in the potential energy surfaces of DHSF (six conformers) and DHSP (seven conformers). The key feature in their molecular structure is the occurrence of intramolecular hydrogen bonding between the hydroxyl and aminocarbonyl groups. We have estimated the strength of each individual hydrogen bond in the mentioned species using the descriptors proposed by three different methodologies, i.e., the quantum theory of atoms in molecules (QTAIM), the natural bond orbitals population analysis (NBO), and the so-called empirical Rozenberg's enthalpy-distance relationship. We have found a good correlation among the calculated values for the different descriptors within the whole set of conformers in the molecular systems in this study. We have also discussed the predicted order of stabilities of the different conformers of each species in terms of the so-called ring anomeric effect (RAE) and generalized anomeric effect (GAE). Finally, we also analyzed the discrepancies found in the order of stability when going from the isolated molecule approximation to water solution (PCM).

  20. Image Descriptors for Displays

    DTIC Science & Technology

    1977-02-01

    information. In Section V of the report, however, we have extended our descriptor for the total channel capacity of a display to include both chromi - nance and...frequency and for constant chromi - nance. The quantities nl(w) represent the number of perceivable colors for a given spatial frequancy and luminance value...the chromi - nance contribution to the total channel capacity, we shall utilize a linear model for thot distribution of perceived chrominance levels. We

  1. Alternative methods for estimating common descriptors for QSAR studies of dyes and fluorescent probes using molecular modeling software. 2. Correlations between log P and the hydrophilic/lipophilic index, and new methods for estimating degrees of amphiphilicity.

    PubMed

    Dapson, Richard W; Horobin, Richard W

    2013-11-01

    The log P descriptor, despite its usefulness, can be difficult to use, especially for researchers lacking skills in physical chemistry. Moreover this classic measure has been determined in numerous ways, which can result in inconsistant estimates of log P values, especially for relatively complex molecules such as fluorescent probes. Novel measures of hydrophilicity/lipophilicity (the Hydrophilic/Lipophilic Index, HLI) and amphiphilicity (hydrophilic/lipophilic indices for the head group and tail, HLIT and HLIHG, respectively) therefore have been devised. We compare these descriptors with measures based on log P, the standard method for quantitative structure activity relationships (QSAR) studies. HLI can be determined using widely available molecular modeling software, coupled with simple arithmetic calculations. It is based on partial atomic charges and is intended to be a stand-alone measure of hydrophilicity/lipophilicity. Given the wide application of log P, however, we investigated the correlation between HLI and log P using a test set of 56 fluorescent probes of widely different physicochemical character. Overall correlation was poor; however, correlation of HLI and log P for probes of narrowly specified charge types, i.e., non-ionic compounds, anions, conjugated cations, or zwitterions, was excellent. Values for probes with additional nonconjugated quaternary cations, however, were less well correlated. The newly devised HLI can be divided into domain-specific descriptors, HLIT and HLIHG in amphiphilic probes. Determinations of amphiphilicity, made independently by the authors using their respective methods, showed excellent agreement. Quantifying amphiphilicity from partial log P values of the head group (head group hydrophilicity; HGH) and tail (amphiphilicity index; AI) has proved useful for understanding fluorescent probe action. The same limitations of log P apply to HGH and AI, however. The novel descriptors, HLIT and HLIHG, offer analogous advantages

  2. 3D Printed Block Copolymer Nanostructures

    ERIC Educational Resources Information Center

    Scalfani, Vincent F.; Turner, C. Heath; Rupar, Paul A.; Jenkins, Alexander H.; Bara, Jason E.

    2015-01-01

    The emergence of 3D printing has dramatically advanced the availability of tangible molecular and extended solid models. Interestingly, there are few nanostructure models available both commercially and through other do-it-yourself approaches such as 3D printing. This is unfortunate given the importance of nanotechnology in science today. In this…

  3. Hough transform-based 3D mesh retrieval

    NASA Astrophysics Data System (ADS)

    Zaharia, Titus; Preteux, Francoise J.

    2001-11-01

    This papre addresses the issue of 3D mesh indexation by using shape descriptors (SDs) under constraints of geometric and topological invariance. A new shape descriptor, the Optimized 3D Hough Transform Descriptor (O3HTD) is here proposed. Intrinsically topologically stable, the O3DHTD is not invariant to geometric transformations. Nevertheless, we show mathematically how the O3DHTD can be optimally associated (in terms of compactness of representation and computational complexity) with a spatial alignment procedure which leads to a geometric invariant behavior. Experimental results have been carried out upon the MPEG-7 3D model database consisting of about 1300 meshes in VRML 2.0 format. Objective retrieval results, based upon the definition of a categorized ground truth subset, are reported in terms of Bull Eye Percentage (BEP) score and compared to those obtained by applying the MPEg-7 3D SD. It is shown that the O3DHTD outperforms the MPEg-7 3D SD of up to 28%.

  4. New developments in PEST shape/property hybrid descriptors

    NASA Astrophysics Data System (ADS)

    Breneman, Curt M.; Sundling, C. Matthew; Sukumar, N.; Shen, Lingling; Katt, William P.; Embrechts, Mark J.

    2003-02-01

    Recent investigations have shown that the inclusion of hybrid shape/property descriptors together with 2D topological descriptors increases the predictive capability of QSAR and QSPR models. Property-Encoded Surface Translator (PEST) descriptors may be computed using ab initio or semi-empirical electron density surfaces and/or electronic properties, as well as atomic fragment-based TAE/RECON property-encoded surface reconstructions. The RECON and PEST algorithms also include rapid fragment-based wavelet coefficient descriptor (WCD) computation. These descriptors enable a compact encoding of chemical information. We also briefly discuss the use of the RECON/PEST methodology in a virtual high-throughput mode, as well as the use of TAE properties for molecular surface autocorrelation analysis.

  5. 3-D Seismic Interpretation

    NASA Astrophysics Data System (ADS)

    Moore, Gregory F.

    2009-05-01

    This volume is a brief introduction aimed at those who wish to gain a basic and relatively quick understanding of the interpretation of three-dimensional (3-D) seismic reflection data. The book is well written, clearly illustrated, and easy to follow. Enough elementary mathematics are presented for a basic understanding of seismic methods, but more complex mathematical derivations are avoided. References are listed for readers interested in more advanced explanations. After a brief introduction, the book logically begins with a succinct chapter on modern 3-D seismic data acquisition and processing. Standard 3-D acquisition methods are presented, and an appendix expands on more recent acquisition techniques, such as multiple-azimuth and wide-azimuth acquisition. Although this chapter covers the basics of standard time processing quite well, there is only a single sentence about prestack depth imaging, and anisotropic processing is not mentioned at all, even though both techniques are now becoming standard.

  6. Radiochromic 3D Detectors

    NASA Astrophysics Data System (ADS)

    Oldham, Mark

    2015-01-01

    Radiochromic materials exhibit a colour change when exposed to ionising radiation. Radiochromic film has been used for clinical dosimetry for many years and increasingly so recently, as films of higher sensitivities have become available. The two principle advantages of radiochromic dosimetry include greater tissue equivalence (radiologically) and the lack of requirement for development of the colour change. In a radiochromic material, the colour change arises direct from ionising interactions affecting dye molecules, without requiring any latent chemical, optical or thermal development, with important implications for increased accuracy and convenience. It is only relatively recently however, that 3D radiochromic dosimetry has become possible. In this article we review recent developments and the current state-of-the-art of 3D radiochromic dosimetry, and the potential for a more comprehensive solution for the verification of complex radiation therapy treatments, and 3D dose measurement in general.

  7. Combined 3D-QSAR, Molecular Docking and Molecular Dynamics Study on Derivatives of Peptide Epoxyketone and Tyropeptin-Boronic Acid as Inhibitors Against the β5 Subunit of Human 20S Proteasome

    PubMed Central

    Liu, Jianling; Zhang, Hong; Xiao, Zhengtao; Wang, Fangfang; Wang, Xia; Wang, Yonghua

    2011-01-01

    An abnormal ubiquitin-proteasome is found in many human diseases, especially in cancer, and has received extensive attention as a promising therapeutic target in recent years. In this work, several in silico models have been built with two classes of proteasome inhibitors (PIs) by using 3D-QSAR, homology modeling, molecular docking and molecular dynamics (MD) simulations. The study resulted in two types of satisfactory 3D-QSAR models, i.e., the CoMFA model (Q2 = 0.462, R2pred = 0.820) for epoxyketone inhibitors (EPK) and the CoMSIA model (Q2 = 0.622, R2pred = 0.821) for tyropeptin-boronic acid derivatives (TBA). From the contour maps, some key structural factors responsible for the activity of these two series of PIs are revealed. For EPK inhibitors, the N-cap part should have higher electropositivity; a large substituent such as a benzene ring is favored at the C6-position. In terms of TBA inhibitors, hydrophobic substituents with a larger size anisole group are preferential at the C8-position; higher electropositive substituents like a naphthalene group at the C3-position can enhance the activity of the drug by providing hydrogen bond interaction with the protein target. Molecular docking disclosed that residues Thr60, Thr80, Gly106 and Ser189 play a pivotal role in maintaining the drug-target interactions, which are consistent with the contour maps. MD simulations further indicated that the binding modes of each conformation derived from docking is stable and in accord with the corresponding structure extracted from MD simulation overall. These results can offer useful theoretical references for designing more potent PIs. PMID:21673924

  8. Evaluation of the EVA descriptor for QSAR studies: 3. The use of a genetic algorithm to search for models with enhanced predictive properties (EVA_GA)

    NASA Astrophysics Data System (ADS)

    Turner, David B.; Willett, Peter

    2000-01-01

    The EVA structural descriptor, based upon calculated fundamental molecular vibrational frequencies, has proved to be an effective descriptor for both QSAR and database similarity calculations. The descriptor is sensitive to 3D structure but has an advantage over field-based 3D-QSAR methods inasmuch as structural superposition is not required. The original technique involves a standardisation method wherein uniform Gaussians of fixed standard deviation (σ) are used to smear out frequencies projected onto a linear scale. The smearing function permits the overlap of proximal frequencies and thence the extraction of a fixed dimensional descriptor regardless of the number and precise values of the frequencies. It is proposed here that there exist optimal localised values of σ in different spectral regions; that is, the overlap of frequencies using uniform Gaussians may, at certain points in the spectrum, either be insufficient to pick up relationships where they exist or mix up information to such an extent that significant correlations are obscured by noise. A genetic algorithm is used to search for optimal localised σ values using crossvalidated PLS regression scores as the fitness score to be optimised. The resultant models were then validated against a previously unseen test set of compounds and through data scrambling. The performance of EVA_GA is compared to that of EVA and analogous CoMFA studies; in the latter case a brief evaluation is made of the effect of grid resolution upon the stability of CoMFA PLS scores particularly in relation to test set predictions.

  9. Bootstrapping 3D fermions

    DOE PAGES

    Iliesiu, Luca; Kos, Filip; Poland, David; ...

    2016-03-17

    We study the conformal bootstrap for a 4-point function of fermions <ψψψψ> in 3D. We first introduce an embedding formalism for 3D spinors and compute the conformal blocks appearing in fermion 4-point functions. Using these results, we find general bounds on the dimensions of operators appearing in the ψ × ψ OPE, and also on the central charge CT. We observe features in our bounds that coincide with scaling dimensions in the GrossNeveu models at large N. Finally, we also speculate that other features could coincide with a fermionic CFT containing no relevant scalar operators.

  10. Bootstrapping 3D fermions

    SciTech Connect

    Iliesiu, Luca; Kos, Filip; Poland, David; Pufu, Silviu S.; Simmons-Duffin, David; Yacoby, Ran

    2016-03-17

    We study the conformal bootstrap for a 4-point function of fermions <ψψψψ> in 3D. We first introduce an embedding formalism for 3D spinors and compute the conformal blocks appearing in fermion 4-point functions. Using these results, we find general bounds on the dimensions of operators appearing in the ψ × ψ OPE, and also on the central charge CT. We observe features in our bounds that coincide with scaling dimensions in the GrossNeveu models at large N. Finally, we also speculate that other features could coincide with a fermionic CFT containing no relevant scalar operators.

  11. Complementing ultrafast shape recognition with an optical isomerism descriptor.

    PubMed

    Zhou, Ting; Lafleur, Karine; Caflisch, Amedeo

    2010-11-01

    We introduce the mixed product of three vectors spanning four molecular locations as a descriptor of optical isomerism. This descriptor is very efficient as it does not require molecular superposition, and is very robust in discriminating between a given isomer and its mirror image. In particular, conformational isomers that are mirror images of each other, as well as optical isomers have opposite sign of the descriptor value. For efficient database searches, the optical isomerism descriptor can be used to complement an available ultrafast shape recognition (USR) method based solely on distances, which is not able to distinguish enantiomers. By an extensive comparison of the USR-based similarity score with an approach based on Gaussian molecular volume overlap, the accuracy and completeness of the former are discussed.

  12. 3D-graphite structure

    SciTech Connect

    Belenkov, E. A. Ali-Pasha, V. A.

    2011-01-15

    The structure of clusters of some new carbon 3D-graphite phases have been calculated using the molecular-mechanics methods. It is established that 3D-graphite polytypes {alpha}{sub 1,1}, {alpha}{sub 1,3}, {alpha}{sub 1,5}, {alpha}{sub 2,1}, {alpha}{sub 2,3}, {alpha}{sub 3,1}, {beta}{sub 1,2}, {beta}{sub 1,4}, {beta}{sub 1,6}, {beta}{sub 2,1}, and {beta}{sub 3,2} consist of sp{sup 2}-hybridized atoms, have hexagonal unit cells, and differ in regards to the structure of layers and order of their alternation. A possible way to experimentally synthesize new carbon phases is proposed: the polymerization and carbonization of hydrocarbon molecules.

  13. Use of molecular modeling, docking, and 3D-QSAR studies for the determination of the binding mode of benzofuran-3-yl-(indol-3-yl)maleimides as GSK-3beta inhibitors.

    PubMed

    Kim, Ki Hwan; Gaisina, Irina; Gallier, Franck; Holzle, Denise; Blond, Sylvie Y; Mesecar, Andrew; Kozikowski, Alan P

    2009-12-01

    Molecular modeling and docking studies along with three-dimensional quantitative structure relationships (3D-QSAR) studies have been used to determine the correct binding mode of glycogen synthase kinase 3beta (GSK-3beta) inhibitors. The approaches of comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) are used for the 3D-QSAR of 51 substituted benzofuran-3-yl-(indol-3-yl)maleimides as GSK-3beta inhibitors. Two binding modes of the inhibitors to the binding site of GSK-3beta are investigated. The binding mode 1 yielded better 3D-QSAR correlations using both CoMFA and CoMSIA methodologies. The three-component CoMFA model from the steric and electrostatic fields for the experimentally determined pIC(50) values has the following statistics: R(2)(cv) = 0.386 nd SE(cv) = 0.854 for the cross-validation, and R(2) = 0.811 and SE = 0.474 for the fitted correlation. F (3,47) = 67.034, and probability of R(2) = 0 (3,47) = 0.000. The binding mode suggested by the results of this study is consistent with the preliminary results of X-ray crystal structures of inhibitor-bound GSK-3beta. The 3D-QSAR models were used for the estimation of the inhibitory potency of two additional compounds.

  14. Venus in 3D

    NASA Technical Reports Server (NTRS)

    Plaut, Jeffrey J.

    1993-01-01

    Stereographic images of the surface of Venus which enable geologists to reconstruct the details of the planet's evolution are discussed. The 120-meter resolution of these 3D images make it possible to construct digital topographic maps from which precise measurements can be made of the heights, depths, slopes, and volumes of geologic structures.

  15. 3D photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Carson, Jeffrey J. L.; Roumeliotis, Michael; Chaudhary, Govind; Stodilka, Robert Z.; Anastasio, Mark A.

    2010-06-01

    Our group has concentrated on development of a 3D photoacoustic imaging system for biomedical imaging research. The technology employs a sparse parallel detection scheme and specialized reconstruction software to obtain 3D optical images using a single laser pulse. With the technology we have been able to capture 3D movies of translating point targets and rotating line targets. The current limitation of our 3D photoacoustic imaging approach is its inability ability to reconstruct complex objects in the field of view. This is primarily due to the relatively small number of projections used to reconstruct objects. However, in many photoacoustic imaging situations, only a few objects may be present in the field of view and these objects may have very high contrast compared to background. That is, the objects have sparse properties. Therefore, our work had two objectives: (i) to utilize mathematical tools to evaluate 3D photoacoustic imaging performance, and (ii) to test image reconstruction algorithms that prefer sparseness in the reconstructed images. Our approach was to utilize singular value decomposition techniques to study the imaging operator of the system and evaluate the complexity of objects that could potentially be reconstructed. We also compared the performance of two image reconstruction algorithms (algebraic reconstruction and l1-norm techniques) at reconstructing objects of increasing sparseness. We observed that for a 15-element detection scheme, the number of measureable singular vectors representative of the imaging operator was consistent with the demonstrated ability to reconstruct point and line targets in the field of view. We also observed that the l1-norm reconstruction technique, which is known to prefer sparseness in reconstructed images, was superior to the algebraic reconstruction technique. Based on these findings, we concluded (i) that singular value decomposition of the imaging operator provides valuable insight into the capabilities of

  16. A systematic approach to prioritize drug targets using machine learning, a molecular descriptor-based classification model, and high-throughput screening of plant derived molecules: a case study in oral cancer.

    PubMed

    Randhawa, Vinay; Kumar Singh, Anil; Acharya, Vishal

    2015-12-01

    Systems-biology inspired identification of drug targets and machine learning-based screening of small molecules which modulate their activity have the potential to revolutionize modern drug discovery by complementing conventional methods. To utilize the effectiveness of such pipelines, we first analyzed the dysregulated gene pairs between control and tumor samples and then implemented an ensemble-based feature selection approach to prioritize targets in oral squamous cell carcinoma (OSCC) for therapeutic exploration. Based on the structural information of known inhibitors of CXCR4-one of the best targets identified in this study-a feature selection was implemented for the identification of optimal structural features (molecular descriptor) based on which a classification model was generated. Furthermore, the CXCR4-centered descriptor-based classification model was finally utilized to screen a repository of plant derived small-molecules to obtain potential inhibitors. The application of our methodology may assist effective selection of the best targets which may have previously been overlooked, that in turn will lead to the development of new oral cancer medications. The small molecules identified in this study can be ideal candidates for trials as potential novel anti-oral cancer agents. Importantly, distinct steps of this whole study may provide reference for the analysis of other complex human diseases.

  17. An Automatic Registration Algorithm for 3D Maxillofacial Model

    NASA Astrophysics Data System (ADS)

    Qiu, Luwen; Zhou, Zhongwei; Guo, Jixiang; Lv, Jiancheng

    2016-09-01

    3D image registration aims at aligning two 3D data sets in a common coordinate system, which has been widely used in computer vision, pattern recognition and computer assisted surgery. One challenging problem in 3D registration is that point-wise correspondences between two point sets are often unknown apriori. In this work, we develop an automatic algorithm for 3D maxillofacial models registration including facial surface model and skull model. Our proposed registration algorithm can achieve a good alignment result between partial and whole maxillofacial model in spite of ambiguous matching, which has a potential application in the oral and maxillofacial reparative and reconstructive surgery. The proposed algorithm includes three steps: (1) 3D-SIFT features extraction and FPFH descriptors construction; (2) feature matching using SAC-IA; (3) coarse rigid alignment and refinement by ICP. Experiments on facial surfaces and mandible skull models demonstrate the efficiency and robustness of our algorithm.

  18. Quantifying the fingerprint descriptor dependence of structure-activity relationship information on a large scale.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2013-09-23

    It is well-known that different molecular representations, e.g., graphs, numerical descriptors, fingerprints, or 3D models, change the numerical results of molecular similarity calculations. Because the assessment of structure-activity relationships (SARs) requires similarity and potency comparisons of active compounds, this representation dependence inevitably also affects SAR analysis. But to what extent? How exactly does SAR information change when alternative fingerprints are used as descriptors? What is the proportion of active compounds with substantial changes in SAR information induced by different fingerprints? To provide answers to these questions, we have quantified changes in SAR information across many different compound classes using six different fingerprints. SAR profiling was carried out on 128 target-based data sets comprising more than 60,000 compounds with high-confidence activity annotations. A numerical measure of SAR discontinuity was applied to assess SAR information on a per compound basis. For ~70% of all test compounds, changes in SAR characteristics were detected when different fingerprints were used as molecular representations. Moreover, the SAR phenotype of ~30% of the compounds changed, and distinct fingerprint-dependent local SAR environments were detected. The fingerprints we compared were found to generate SAR models that were essentially not comparable. Atom environment and pharmacophore fingerprints produced the largest differences in compound-associated SAR information. Taken together, the results of our systematic analysis reveal larger fingerprint-dependent changes in compound-associated SAR information than would have been anticipated.

  19. Molecular tectonics: control of pore size and polarity in 3-D hexagonal coordination networks based on porphyrins and a zinc cation.

    PubMed

    Kühn, Elisabeth; Bulach, Véronique; Hosseini, Mir Wais

    2008-11-07

    In the crystalline phase, porphyrin derivatives based on two 4-pyridyl units at the 5 and 15 meso positions and two 4-aryl moieties bearing various groups (CN, OMe, OH and CF(3)) at the 10 and 20 meso positions lead, in the presence of a zinc dication, to the formation of robust 3-D networks presenting hexagonal channels: both the size and the polarity of the pores were tuned by the nature of the substituents attached to the two aryl groups.

  20. 3D-QSAR and docking studies on 4-anilinoquinazoline and 4-anilinoquinoline epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors

    NASA Astrophysics Data System (ADS)

    Assefa, Haregewein; Kamath, Shantaram; Buolamwini, John K.

    2003-08-01

    The overexpression and/or mutation of the epidermal growth factor receptor (EGFR) tyrosine kinase has been observed in many human solid tumors, and is under intense investigation as a novel anticancer molecular target. Comparative 3D-QSAR analyses using different alignments were undertaken employing comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) for 122 anilinoquinazoline and 50 anilinoquinoline inhibitors of EGFR kinase. The SYBYL multifit alignment rule was applied to three different conformational templates, two obtained from a MacroModel Monte Carlo conformational search, and one from the bound conformation of erlotinib in complex with EGFR in the X-ray crystal structure. In addition, a flexible ligand docking alignment obtained with the GOLD docking program, and a novel flexible receptor-guided consensus dynamics alignment obtained with the DISCOVER program in the INSIGHTII modeling package were also investigated. 3D-QSAR models with q2 values up to 0.70 and r2 values up to 0.97 were obtained. Among the 4-anilinoquinazoline set, the q2 values were similar, but the ability of the different conformational models to predict the activities of an external test set varied considerably. In this regard, the model derived using the X-ray crystallographically determined bioactive conformation of erlotinib afforded the best predictive model. Electrostatic, hydrophobic and H-bond donor descriptors contributed the most to the QSAR models of the 4-anilinoquinazolines, whereas electrostatic, hydrophobic and H-bond acceptor descriptors contributed the most to the 4-anilinoquinoline QSAR, particularly the H-bond acceptor descriptor. A novel receptor-guided consensus dynamics alignment has also been introduced for 3D-QSAR studies. This new alignment method may incorporate to some extent ligand-receptor induced fit effects into 3D-QSAR models.

  1. Face recognition based on matching of local features on 3D dynamic range sequences

    NASA Astrophysics Data System (ADS)

    Echeagaray-Patrón, B. A.; Kober, Vitaly

    2016-09-01

    3D face recognition has attracted attention in the last decade due to improvement of technology of 3D image acquisition and its wide range of applications such as access control, surveillance, human-computer interaction and biometric identification systems. Most research on 3D face recognition has focused on analysis of 3D still data. In this work, a new method for face recognition using dynamic 3D range sequences is proposed. Experimental results are presented and discussed using 3D sequences in the presence of pose variation. The performance of the proposed method is compared with that of conventional face recognition algorithms based on descriptors.

  2. 3D in-vivo imaging of GFP-expressing T-cells in mice with non-contact fluorescence molecular tomography (Invited Paper)

    NASA Astrophysics Data System (ADS)

    Garofalakis, Anikitos; Meyer, Heiko; Zacharakis, Giannis; Economou, Eleftherios N.; Mamalaki, Clio; Papamatheakis, Joseph; Ntziachristos, Vasilis; Ripoll, Jorge

    2005-06-01

    Optical imaging and tomography in tissues can facilitate the quantitative study of several important chromophores and fluorophores in-vivo. Due to this fact, there has been great interest in developing imaging systems offering quantitative information on the location and concentration of chromophores and fluorescent probes. In this study we present a novel imaging system that enables three dimensional (3D) imaging of fluorescent signals in bodies of arbitrary shapes in a non-contact geometry, in combination with a 3D surface reconstruction algorithm, which is appropriate for in-vivo small animal imaging of fluorescent probes. The system consists of a rotating sample holder and a lens coupled Charge Coupled Device (CCD) camera in combination with a fiber coupled laser scanning device. An Argon ion laser is used as the source and different filters are used for the detection of various fluorophores or fluorescing proteins. With this new setup a large measurements dataset can be achieved while the use of inversion models give a high capacity for quantitative 3D reconstruction of fluorochrome distributions as well as high spatial resolution. The system has already been tested in the observation of the distribution of Green Fluorescent Protein (GFP) expressing T-lymphocytes in order to study the function of the immune system in a murine model, which can then be related to the function of the human immune system.

  3. Visual Semantic Based 3D Video Retrieval System Using HDFS

    PubMed Central

    Kumar, C.Ranjith; Suguna, S.

    2016-01-01

    This paper brings out a neoteric frame of reference for visual semantic based 3d video search and retrieval applications. Newfangled 3D retrieval application spotlight on shape analysis like object matching, classification and retrieval not only sticking up entirely with video retrieval. In this ambit, we delve into 3D-CBVR (Content Based Video Retrieval) concept for the first time. For this purpose, we intent to hitch on BOVW and Mapreduce in 3D framework. Instead of conventional shape based local descriptors, we tried to coalesce shape, color and texture for feature extraction. For this purpose, we have used combination of geometric & topological features for shape and 3D co-occurrence matrix for color and texture. After thriving extraction of local descriptors, TB-PCT (Threshold Based- Predictive Clustering Tree) algorithm is used to generate visual codebook and histogram is produced. Further, matching is performed using soft weighting scheme with L2 distance function. As a final step, retrieved results are ranked according to the Index value and acknowledged to the user as a feedback .In order to handle prodigious amount of data and Efficacious retrieval, we have incorporated HDFS in our Intellection. Using 3D video dataset, we future the performance of our proposed system which can pan out that the proposed work gives meticulous result and also reduce the time intricacy. PMID:28003793

  4. Visual Semantic Based 3D Video Retrieval System Using HDFS.

    PubMed

    Kumar, C Ranjith; Suguna, S

    2016-08-01

    This paper brings out a neoteric frame of reference for visual semantic based 3d video search and retrieval applications. Newfangled 3D retrieval application spotlight on shape analysis like object matching, classification and retrieval not only sticking up entirely with video retrieval. In this ambit, we delve into 3D-CBVR (Content Based Video Retrieval) concept for the first time. For this purpose, we intent to hitch on BOVW and Mapreduce in 3D framework. Instead of conventional shape based local descriptors, we tried to coalesce shape, color and texture for feature extraction. For this purpose, we have used combination of geometric & topological features for shape and 3D co-occurrence matrix for color and texture. After thriving extraction of local descriptors, TB-PCT (Threshold Based- Predictive Clustering Tree) algorithm is used to generate visual codebook and histogram is produced. Further, matching is performed using soft weighting scheme with L2 distance function. As a final step, retrieved results are ranked according to the Index value and acknowledged to the user as a feedback .In order to handle prodigious amount of data and Efficacious retrieval, we have incorporated HDFS in our Intellection. Using 3D video dataset, we future the performance of our proposed system which can pan out that the proposed work gives meticulous result and also reduce the time intricacy.

  5. LigandBox: A database for 3D structures of chemical compounds.

    PubMed

    Kawabata, Takeshi; Sugihara, Yusuke; Fukunishi, Yoshifumi; Nakamura, Haruki

    2013-01-01

    A database for the 3D structures of available compounds is essential for the virtual screening by molecular docking. We have developed the LigandBox database (http://ligandbox.protein.osaka-u.ac.jp/ligandbox/) containing four million available compounds, collected from the catalogues of 37 commercial suppliers, and approved drugs and biochemical compounds taken from KEGG_DRUG, KEGG_COMPOUND and PDB databases. Each chemical compound in the database has several 3D conformers with hydrogen atoms and atomic charges, which are ready to be docked into receptors using docking programs. The 3D conformations were generated using our molecular simulation program package, myPresto. Various physical properties, such as aqueous solubility (LogS) and carcinogenicity have also been calculated to characterize the ADME-Tox properties of the compounds. The Web database provides two services for compound searches: a property/chemical ID search and a chemical structure search. The chemical structure search is performed by a descriptor search and a maximum common substructure (MCS) search combination, using our program kcombu. By specifying a query chemical structure, users can find similar compounds among the millions of compounds in the database within a few minutes. Our database is expected to assist a wide range of researchers, in the fields of medical science, chemical biology, and biochemistry, who are seeking to discover active chemical compounds by the virtual screening.

  6. A spherical harmonics intensity model for 3D segmentation and 3D shape analysis of heterochromatin foci.

    PubMed

    Eck, Simon; Wörz, Stefan; Müller-Ott, Katharina; Hahn, Matthias; Biesdorf, Andreas; Schotta, Gunnar; Rippe, Karsten; Rohr, Karl

    2016-08-01

    The genome is partitioned into regions of euchromatin and heterochromatin. The organization of heterochromatin is important for the regulation of cellular processes such as chromosome segregation and gene silencing, and their misregulation is linked to cancer and other diseases. We present a model-based approach for automatic 3D segmentation and 3D shape analysis of heterochromatin foci from 3D confocal light microscopy images. Our approach employs a novel 3D intensity model based on spherical harmonics, which analytically describes the shape and intensities of the foci. The model parameters are determined by fitting the model to the image intensities using least-squares minimization. To characterize the 3D shape of the foci, we exploit the computed spherical harmonics coefficients and determine a shape descriptor. We applied our approach to 3D synthetic image data as well as real 3D static and real 3D time-lapse microscopy images, and compared the performance with that of previous approaches. It turned out that our approach yields accurate 3D segmentation results and performs better than previous approaches. We also show that our approach can be used for quantifying 3D shape differences of heterochromatin foci.

  7. Twin Peaks - 3D

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The two hills in the distance, approximately one to two kilometers away, have been dubbed the 'Twin Peaks' and are of great interest to Pathfinder scientists as objects of future study. 3D glasses are necessary to identify surface detail. The white areas on the left hill, called the 'Ski Run' by scientists, may have been formed by hydrologic processes.

    The IMP is a stereo imaging system with color capability provided by 24 selectable filters -- twelve filters per 'eye.

    Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  8. 3D and beyond

    NASA Astrophysics Data System (ADS)

    Fung, Y. C.

    1995-05-01

    This conference on physiology and function covers a wide range of subjects, including the vasculature and blood flow, the flow of gas, water, and blood in the lung, the neurological structure and function, the modeling, and the motion and mechanics of organs. Many technologies are discussed. I believe that the list would include a robotic photographer, to hold the optical equipment in a precisely controlled way to obtain the images for the user. Why are 3D images needed? They are to achieve certain objectives through measurements of some objects. For example, in order to improve performance in sports or beauty of a person, we measure the form, dimensions, appearance, and movements.

  9. 3D Audio System

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Ames Research Center research into virtual reality led to the development of the Convolvotron, a high speed digital audio processing system that delivers three-dimensional sound over headphones. It consists of a two-card set designed for use with a personal computer. The Convolvotron's primary application is presentation of 3D audio signals over headphones. Four independent sound sources are filtered with large time-varying filters that compensate for motion. The perceived location of the sound remains constant. Possible applications are in air traffic control towers or airplane cockpits, hearing and perception research and virtual reality development.

  10. Statistically validated QSARs, based on theoretical descriptors, for modeling aquatic toxicity of organic chemicals in Pimephales promelas (fathead minnow).

    PubMed

    Papa, Ester; Villa, Fulvio; Gramatica, Paola

    2005-01-01

    The use of Quantitative Structure-Activity Relationships in assessing the potential negative effects of chemicals plays an important role in ecotoxicology. (LC50)(96h) in Pimephales promelas (Duluth database) is widely modeled as an aquatic toxicity end-point. The object of this study was to compare different molecular descriptors in the development of new statistically validated QSAR models to predict the aquatic toxicity of chemicals classified according to their MOA and in a unique general model. The applied multiple linear regression approach (ordinary least squares) is based on theoretical molecular descriptor variety (1D, 2D, and 3D, from DRAGON package, and some calculated logP). The best combination of modeling descriptors was selected by the Genetic Algorithm-Variable Subset Selection procedure. The robustness and the predictive performance of the proposed models was verified using both internal (cross-validation by LOO, bootstrap, Y-scrambling) and external statistical validations (by splitting the original data set into training and validation sets by Kohonen-artificial neural networks (K-ANN)). The model applicability domain (AD) was checked by the leverage approach to verify prediction reliability.

  11. Physicochemical vs. Vibrational Descriptors for Prediction of Odor Receptor Responses.

    PubMed

    Gabler, Stephan; Soelter, Jan; Hussain, Taufia; Sachse, Silke; Schmuker, Michael

    2013-10-01

    Responses of olfactory receptors (ORs) can be predicted by applying machine learning methods on a multivariate encoding of an odorant's chemical structure. Physicochemical descriptors that encode features of the molecular graph are a popular choice for such an encoding. Here, we explore the EVA descriptor set, which encodes features derived from the vibrational spectrum of a molecule. We assessed the performance of Support Vector Regression (SVR) and Random Forest Regression (RFR) to predict the gradual response of Drosophila ORs. We compared a 27-dimensional variant of the EVA descriptor against a set of 1467 descriptors provided by the eDragon software package, and against a 32-dimensional subset thereof that has been proposed as the basis for an odor metric consisting of 32 descriptors (HADDAD). The best prediction performance was reproducibly achieved using SVR on the highest-dimensional feature set. The low-dimensional EVA and HADDAD feature sets predicted odor-OR interactions with similar accuracy. Adding charge and polarizability information to the EVA descriptor did not improve the results but rather decreased predictive power. Post-hoc in vivo measurements confirmed these results. Our findings indicate that EVA provides a meaningful low-dimensional representation of odor space, although EVA hardly outperformed "classical" descriptor sets.

  12. 3D Surgical Simulation

    PubMed Central

    Cevidanes, Lucia; Tucker, Scott; Styner, Martin; Kim, Hyungmin; Chapuis, Jonas; Reyes, Mauricio; Proffit, William; Turvey, Timothy; Jaskolka, Michael

    2009-01-01

    This paper discusses the development of methods for computer-aided jaw surgery. Computer-aided jaw surgery allows us to incorporate the high level of precision necessary for transferring virtual plans into the operating room. We also present a complete computer-aided surgery (CAS) system developed in close collaboration with surgeons. Surgery planning and simulation include construction of 3D surface models from Cone-beam CT (CBCT), dynamic cephalometry, semi-automatic mirroring, interactive cutting of bone and bony segment repositioning. A virtual setup can be used to manufacture positioning splints for intra-operative guidance. The system provides further intra-operative assistance with the help of a computer display showing jaw positions and 3D positioning guides updated in real-time during the surgical procedure. The CAS system aids in dealing with complex cases with benefits for the patient, with surgical practice, and for orthodontic finishing. Advanced software tools for diagnosis and treatment planning allow preparation of detailed operative plans, osteotomy repositioning, bone reconstructions, surgical resident training and assessing the difficulties of the surgical procedures prior to the surgery. CAS has the potential to make the elaboration of the surgical plan a more flexible process, increase the level of detail and accuracy of the plan, yield higher operative precision and control, and enhance documentation of cases. Supported by NIDCR DE017727, and DE018962 PMID:20816308

  13. Martian terrain - 3D

    NASA Technical Reports Server (NTRS)

    1997-01-01

    An area of rocky terrain near the landing site of the Sagan Memorial Station can be seen in this image, taken in stereo by the Imager for Mars Pathfinder (IMP) on Sol 3. 3D glasses are necessary to identify surface detail. This image is part of a 3D 'monster' panorama of the area surrounding the landing site.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

    Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  14. The NIH 3D Print Exchange: A Public Resource for Bioscientific and Biomedical 3D Prints

    PubMed Central

    Coakley, Meghan F.; Hurt, Darrell E.; Weber, Nick; Mtingwa, Makazi; Fincher, Erin C.; Alekseyev, Vsevelod; Chen, David T.; Yun, Alvin; Gizaw, Metasebia; Swan, Jeremy; Yoo, Terry S.; Huyen, Yentram

    2016-01-01

    The National Institutes of Health (NIH) has launched the NIH 3D Print Exchange, an online portal for discovering and creating bioscientifically relevant 3D models suitable for 3D printing, to provide both researchers and educators with a trusted source to discover accurate and informative models. There are a number of online resources for 3D prints, but there is a paucity of scientific models, and the expertise required to generate and validate such models remains a barrier. The NIH 3D Print Exchange fills this gap by providing novel, web-based tools that empower users with the ability to create ready-to-print 3D files from molecular structure data, microscopy image stacks, and computed tomography scan data. The NIH 3D Print Exchange facilitates open data sharing in a community-driven environment, and also includes various interactive features, as well as information and tutorials on 3D modeling software. As the first government-sponsored website dedicated to 3D printing, the NIH 3D Print Exchange is an important step forward to bringing 3D printing to the mainstream for scientific research and education. PMID:28367477

  15. Filling the gap between the quantum and classical worlds of nanoscale magnetism: giant molecular aggregates based on paramagnetic 3d metal ions.

    PubMed

    Papatriantafyllopoulou, Constantina; Moushi, Eleni E; Christou, George; Tasiopoulos, Anastasios J

    2016-03-21

    In this review, aspects of the syntheses, structures and magnetic properties of giant 3d and 3d/4f paramagnetic metal clusters in moderate oxidation states are discussed. The term "giant clusters" is used herein to denote metal clusters with nuclearity of 30 or greater. Many synthetic strategies towards such species have been developed and are discussed in this paper. Attempts are made to categorize some of the most successful methods to giant clusters, but it will be pointed out that the characteristics of the crystal structures of such compounds including nuclearity, shape, architecture, etc. are unpredictable depending on the specific structural features of the included organic ligands, reaction conditions and other factors. The majority of the described compounds in this review are of special interest not only for their fascinating nanosized structures but also because they sometimes display interesting magnetic phenomena, such as ferromagnetic exchange interactions, large ground state spin values, single-molecule magnetism behaviour or impressively large magnetocaloric effects. In addition, they often possess the properties of both the quantum and the classical world, and thus their systematic study offers the potential for the discovery of new physical phenomena, as well as a better understanding of the existing ones. The research field of giant clusters is under continuous evolution and their intriguing structural characteristics and magnetism properties that attract the interest of synthetic Inorganic Chemists promise a brilliant future for this class of compounds.

  16. 3D field harmonics

    SciTech Connect

    Caspi, S.; Helm, M.; Laslett, L.J.

    1991-03-30

    We have developed an harmonic representation for the three dimensional field components within the windings of accelerator magnets. The form by which the field is presented is suitable for interfacing with other codes that make use of the 3D field components (particle tracking and stability). The field components can be calculated with high precision and reduced cup time at any location (r,{theta},z) inside the magnet bore. The same conductor geometry which is used to simulate line currents is also used in CAD with modifications more readily available. It is our hope that the format used here for magnetic fields can be used not only as a means of delivering fields but also as a way by which beam dynamics can suggest correction to the conductor geometry. 5 refs., 70 figs.

  17. Self-assembled 3D heterometallic Cu(II)/Fe(II) coordination polymers with octahedral net skeletons: structural features, molecular magnetism, thermal and oxidation catalytic properties.

    PubMed

    Karabach, Yauhen Y; Guedes da Silva, M Fátima C; Kopylovich, Maximilian N; Gil-Hernández, Beatriz; Sanchiz, Joaquin; Kirillov, Alexander M; Pombeiro, Armando J L

    2010-12-06

    The new three-dimensional (3D) heterometallic Cu(II)/Fe(II) coordination polymers [Cu(6)(H(2)tea)(6)Fe(CN)(6)](n)(NO(3))(2n)·6nH(2)O (1) and [Cu(6)(Hmdea)(6)Fe(CN)(6)](n)(NO(3))(2n)·7nH(2)O (2) have been easily generated by aqueous-medium self-assembly reactions of copper(II) nitrate with triethanolamine or N-methyldiethanolamine (H(3)tea or H(2)mdea, respectively), in the presence of potassium ferricyanide and sodium hydroxide. They have been isolated as air-stable crystalline solids and fully characterized including by single-crystal X-ray diffraction analyses. The latter reveal the formation of 3D metal-organic frameworks that are constructed from the [Cu(2)(μ-H(2)tea)(2)](2+) or [Cu(2)(μ-Hmdea)(2)](2+) nodes and the octahedral [Fe(CN)(6)](4-) linkers, featuring regular (1) or distorted (2) octahedral net skeletons. Upon dehydration, both compounds show reversible escape and binding processes toward water or methanol molecules. Magnetic susceptibility measurements of 1 and 2 reveal strong antiferromagnetic [J = -199(1) cm(-1)] or strong ferromagnetic [J = +153(1) cm(-1)] couplings between the copper(II) ions through the μ-O-alkoxo atoms in 1 or 2, respectively. The differences in magnetic behavior are explained in terms of the dependence of the magnetic coupling constant on the Cu-O-Cu bridging angle. Compounds 1 and 2 also act as efficient catalyst precursors for the mild oxidation of cyclohexane by aqueous hydrogen peroxide to cyclohexanol and cyclohexanone (homogeneous catalytic system), leading to maximum total yields (based on cyclohexane) and turnover numbers (TONs) up to about 22% and 470, respectively.

  18. A Theoretical Framework for Lagrangian Descriptors

    NASA Astrophysics Data System (ADS)

    Lopesino, C.; Balibrea-Iniesta, F.; García-Garrido, V. J.; Wiggins, S.; Mancho, A. M.

    This paper provides a theoretical background for Lagrangian Descriptors (LDs). The goal of achieving rigorous proofs that justify the ability of LDs to detect invariant manifolds is simplified by introducing an alternative definition for LDs. The definition is stated for n-dimensional systems with general time dependence, however we rigorously prove that this method reveals the stable and unstable manifolds of hyperbolic points in four particular 2D cases: a hyperbolic saddle point for linear autonomous systems, a hyperbolic saddle point for nonlinear autonomous systems, a hyperbolic saddle point for linear nonautonomous systems and a hyperbolic saddle point for nonlinear nonautonomous systems. We also discuss further rigorous results which show the ability of LDs to highlight additional invariants sets, such as n-tori. These results are just a simple extension of the ergodic partition theory which we illustrate by applying this methodology to well-known examples, such as the planar field of the harmonic oscillator and the 3D ABC flow. Finally, we provide a thorough discussion on the requirement of the objectivity (frame-invariance) property for tools designed to reveal phase space structures and their implications for Lagrangian descriptors.

  19. Intraoral 3D scanner

    NASA Astrophysics Data System (ADS)

    Kühmstedt, Peter; Bräuer-Burchardt, Christian; Munkelt, Christoph; Heinze, Matthias; Palme, Martin; Schmidt, Ingo; Hintersehr, Josef; Notni, Gunther

    2007-09-01

    Here a new set-up of a 3D-scanning system for CAD/CAM in dental industry is proposed. The system is designed for direct scanning of the dental preparations within the mouth. The measuring process is based on phase correlation technique in combination with fast fringe projection in a stereo arrangement. The novelty in the approach is characterized by the following features: A phase correlation between the phase values of the images of two cameras is used for the co-ordinate calculation. This works contrary to the usage of only phase values (phasogrammetry) or classical triangulation (phase values and camera image co-ordinate values) for the determination of the co-ordinates. The main advantage of the method is that the absolute value of the phase at each point does not directly determine the coordinate. Thus errors in the determination of the co-ordinates are prevented. Furthermore, using the epipolar geometry of the stereo-like arrangement the phase unwrapping problem of fringe analysis can be solved. The endoscope like measurement system contains one projection and two camera channels for illumination and observation of the object, respectively. The new system has a measurement field of nearly 25mm × 15mm. The user can measure two or three teeth at one time. So the system can by used for scanning of single tooth up to bridges preparations. In the paper the first realization of the intraoral scanner is described.

  20. 'Diamond' in 3-D

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This 3-D, microscopic imager mosaic of a target area on a rock called 'Diamond Jenness' was taken after NASA's Mars Exploration Rover Opportunity ground into the surface with its rock abrasion tool for a second time.

    Opportunity has bored nearly a dozen holes into the inner walls of 'Endurance Crater.' On sols 177 and 178 (July 23 and July 24, 2004), the rover worked double-duty on Diamond Jenness. Surface debris and the bumpy shape of the rock resulted in a shallow and irregular hole, only about 2 millimeters (0.08 inch) deep. The final depth was not enough to remove all the bumps and leave a neat hole with a smooth floor. This extremely shallow depression was then examined by the rover's alpha particle X-ray spectrometer.

    On Sol 178, Opportunity's 'robotic rodent' dined on Diamond Jenness once again, grinding almost an additional 5 millimeters (about 0.2 inch). The rover then applied its Moessbauer spectrometer to the deepened hole. This double dose of Diamond Jenness enabled the science team to examine the rock at varying layers. Results from those grindings are currently being analyzed.

    The image mosaic is about 6 centimeters (2.4 inches) across.

  1. Prominent rocks - 3D

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Many prominent rocks near the Sagan Memorial Station are featured in this image, taken in stereo by the Imager for Mars Pathfinder (IMP) on Sol 3. 3D glasses are necessary to identify surface detail. Wedge is at lower left; Shark, Half-Dome, and Pumpkin are at center. Flat Top, about four inches high, is at lower right. The horizon in the distance is one to two kilometers away.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

    Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  2. Quantifying modes of 3D cell migration

    PubMed Central

    Driscoll, Meghan K.; Danuser, Gaudenz

    2015-01-01

    Although it is widely appreciated that cells migrate in a variety of diverse environments in vivo, we are only now beginning to use experimental workflows that yield images with sufficient spatiotemporal resolution to study the molecular processes governing cell migration in 3D environments. Since cell migration is a dynamic process, it is usually studied via microscopy, but 3D movies of 3D processes are difficult to interpret by visual inspection. In this review, we discuss the technologies required to study the diversity of 3D cell migration modes with a focus on the visualization and computational analysis tools needed to study cell migration quantitatively at a level comparable to the analyses performed today on cells crawling on flat substrates. PMID:26603943

  3. Modeling cellular processes in 3D.

    PubMed

    Mogilner, Alex; Odde, David

    2011-12-01

    Recent advances in photonic imaging and fluorescent protein technology offer unprecedented views of molecular space-time dynamics in living cells. At the same time, advances in computing hardware and software enable modeling of ever more complex systems, from global climate to cell division. As modeling and experiment become more closely integrated we must address the issue of modeling cellular processes in 3D. Here, we highlight recent advances related to 3D modeling in cell biology. While some processes require full 3D analysis, we suggest that others are more naturally described in 2D or 1D. Keeping the dimensionality as low as possible reduces computational time and makes models more intuitively comprehensible; however, the ability to test full 3D models will build greater confidence in models generally and remains an important emerging area of cell biological modeling.

  4. Quantifying Modes of 3D Cell Migration.

    PubMed

    Driscoll, Meghan K; Danuser, Gaudenz

    2015-12-01

    Although it is widely appreciated that cells migrate in a variety of diverse environments in vivo, we are only now beginning to use experimental workflows that yield images with sufficient spatiotemporal resolution to study the molecular processes governing cell migration in 3D environments. Since cell migration is a dynamic process, it is usually studied via microscopy, but 3D movies of 3D processes are difficult to interpret by visual inspection. In this review, we discuss the technologies required to study the diversity of 3D cell migration modes with a focus on the visualization and computational analysis tools needed to study cell migration quantitatively at a level comparable to the analyses performed today on cells crawling on flat substrates.

  5. A combined pharmacophore modeling, 3D-QSAR and molecular docking study of substituted bicyclo-[3.3.0]oct-2-enes as liver receptor homolog-1 (LRH-1) agonists

    NASA Astrophysics Data System (ADS)

    Lalit, Manisha; Gangwal, Rahul P.; Dhoke, Gaurao V.; Damre, Mangesh V.; Khandelwal, Kanchan; Sangamwar, Abhay T.

    2013-10-01

    A combined pharmacophore modelling, 3D-QSAR and molecular docking approach was employed to reveal structural and chemical features essential for the development of small molecules as LRH-1 agonists. The best HypoGen pharmacophore hypothesis (Hypo1) consists of one hydrogen-bond donor (HBD), two general hydrophobic (H), one hydrophobic aromatic (HYAr) and one hydrophobic aliphatic (HYA) feature. It has exhibited high correlation coefficient of 0.927, cost difference of 85.178 bit and low RMS value of 1.411. This pharmacophore hypothesis was cross-validated using test set, decoy set and Cat-Scramble methodology. Subsequently, validated pharmacophore hypothesis was used in the screening of small chemical databases. Further, 3D-QSAR models were developed based on the alignment obtained using substructure alignment. The best CoMFA and CoMSIA model has exhibited excellent rncv2 values of 0.991 and 0.987, and rcv2 values of 0.767 and 0.703, respectively. CoMFA predicted rpred2 of 0.87 and CoMSIA predicted rpred2 of 0.78 showed that the predicted values were in good agreement with the experimental values. Molecular docking analysis reveals that π-π interaction with His390 and hydrogen bond interaction with His390/Arg393 is essential for LRH-1 agonistic activity. The results from pharmacophore modelling, 3D-QSAR and molecular docking are complementary to each other and could serve as a powerful tool for the discovery of potent small molecules as LRH-1 agonists.

  6. Experimental (FT-IR, FT-Raman, UV and NMR) and quantum chemical studies on molecular structure, spectroscopic analysis, NLO, NBO and reactivity descriptors of 3,5-Difluoroaniline.

    PubMed

    Pathak, S K; Srivastava, R; Sachan, A K; Prasad, O; Sinha, L; Asiri, A M; Karabacak, M

    2015-01-25

    Comprehensive investigation of geometrical and electronic structure in ground as well as the first excited state of 3,5-Difluoroaniline (C6H5NF2) was carried out. The experimentally observed spectral data (FT-TR and FT-Raman) of the title compound was compared with the spectral data obtained by DFT/B3LYP method using 6-311++G(d,p) basis set. The molecular properties like dipole moment, polarizability, first static hyperpolarizability, molecular electrostatic potential surface (MEPs), and contour map were calculated to get a better insight of the properties of the title molecule. Natural bond orbital (NBO) analysis was applied to study stability of the molecule arising from charge delocalization. UV-Vis spectrum of the title compound was also recorded and the electronic properties, such as Frontier orbitals and band gap energies were measured by TD-DFT approach. Total and partial density of state (TDOS and PDOS) and also overlap population density of state (OPDOS) diagrams analysis were presented. Global and local reactivity descriptors were computed to predict reactivity and reactive sites on the molecule. (1)H and (13)C NMR spectra by using gauge including atomic orbital (GIAO) method of studied compound were compared with experimental data obtained. Moreover, the thermodynamic properties were evaluated.

  7. Combining 3-D plasmonic gold nanorod arrays with colloidal nanoparticles as a versatile concept for reliable, sensitive, and selective molecular detection by SERS.

    PubMed

    Yilmaz, Mehmet; Senlik, Erhan; Biskin, Erhan; Yavuz, Mustafa Selman; Tamer, Ugur; Demirel, Gokhan

    2014-03-28

    The detection of molecules at an ultralow level by Surface-Enhanced Raman Spectroscopy (SERS) has recently attracted enormous interest for various applications especially in biological, medical, and environmental fields. Despite the significant progress, SERS systems are still facing challenges for practical applications related to their sensitivity, reliability, and selectivity. To overcome these limitations, in this study, we have proposed a simple yet facile concept by combining 3-D anisotropic gold nanorod arrays with colloidal gold nanoparticles having different shapes for highly reliable, selective, and sensitive detection of some hazardous chemical and biological warfare agents in trace amounts through SERS. The gold nanorod arrays were created on the BK7 glass slides or silicon wafer surfaces via the oblique angle deposition (OAD) technique without using any template material or lithography technique and their surface densities were adjusted by manipulating the deposition angle (α). It is found that gold nanorod arrays fabricated at α = 10° exhibited the highest SERS enhancement in the absence of colloidal gold nanoparticles. Synergetic enhancement was obviously observed in SERS signals when combining gold nanorod arrays with colloidal gold nanoparticles having different shapes (i.e., spherical, rod, and cage). Due to their ability to produce localized surface plasmons (LSPs) in transverse and longitudinal directions, utilization of colloidal gold nanorods as a synergetic agent led to an increase in the enhancement factor by about tenfold compared to plain gold nanorod arrays. Moreover, we have tested our approach to detect some chemical and biological toxins namely dipicolinic acid (DIP), methyl parathion (MP), and diethyl phosphoramidate (DP). For all toxins, Raman spectra with high signal-to-noise ratios and reproducibility were successfully obtained over a broad concentration range (5 ppm-10 ppb). Our results suggest that the slightly tangled and

  8. Molecular cloning of the cDNA encoding the Epstein-Barr virus/C3d receptor (complement receptor type 2) of human B lymphocytes

    SciTech Connect

    Moore, M.D.; Cooper, N.R.; Tack, B.F.; Nemerow, G.R.

    1987-12-01

    Complementary DNA clones for complement receptor type 2 (CR2), the B-lymphocyte membrane protein that serves as the receptor for Epstein-Barr virus and the C3d complement fragment, were obtained by screening a lambda gt11 library generated from Raji B lymphoblastoid cell mRNA. A 4.2-kilobase (kb) clone, representing the entire coding sequence of the protein plus untranslated 5' and 3' nucleotide sequences was obtained and sequenced. The 4.2-kb clone, which contains all but about 500 base pairs (bp) of the 5' untranslated region of the full-length CR2 mRNA, consists of 63 bp of 5' untranslated nucleotide sequence followed successively by a start codon, a 20-amino acid hydrophobic signal peptide, 1005 amino acids having a repeating motif, a 28-amino acid probable transmembrane domain, and a 34-amino acid cytoplasmic tail. The deduced amino acid sequence of the protein indicates that the extracellular domain consists entirely of 16 tandemly arranged repeating elements, each 60-75 amino acids in length, which are identified by multiple conserved residues. This repeating motif also occurs in the C3b/C4b receptor, several complement proteins, and a number of noncomplement proteins. In CR2, the 16 repeats occur in four clusters of four repeats each. Approximately 10% of the deduced amino acid sequence, including the amino and carboxyl termini, was confirmed by amino acid sequencing of tryptic peptides derived from purified CR2. The nucleotide and derived amino acid sequence of CR2 and related studies are presented here.

  9. Massively parallel implementation of 3D-RISM calculation with volumetric 3D-FFT.

    PubMed

    Maruyama, Yutaka; Yoshida, Norio; Tadano, Hiroto; Takahashi, Daisuke; Sato, Mitsuhisa; Hirata, Fumio

    2014-07-05

    A new three-dimensional reference interaction site model (3D-RISM) program for massively parallel machines combined with the volumetric 3D fast Fourier transform (3D-FFT) was developed, and tested on the RIKEN K supercomputer. The ordinary parallel 3D-RISM program has a limitation on the number of parallelizations because of the limitations of the slab-type 3D-FFT. The volumetric 3D-FFT relieves this limitation drastically. We tested the 3D-RISM calculation on the large and fine calculation cell (2048(3) grid points) on 16,384 nodes, each having eight CPU cores. The new 3D-RISM program achieved excellent scalability to the parallelization, running on the RIKEN K supercomputer. As a benchmark application, we employed the program, combined with molecular dynamics simulation, to analyze the oligomerization process of chymotrypsin Inhibitor 2 mutant. The results demonstrate that the massive parallel 3D-RISM program is effective to analyze the hydration properties of the large biomolecular systems.

  10. Insertion of a single-molecule magnet inside a ferromagnetic lattice based on a 3D bimetallic oxalate network: towards molecular analogues of permanent magnets.

    PubMed

    Clemente-León, Miguel; Coronado, Eugenio; Gómez-García, Carlos J; López-Jordà, Maurici; Camón, Agustín; Repollés, Ana; Luis, Fernando

    2014-02-03

    The insertion of the single-molecule magnet (SMM) [Mn(III)(salen)(H2O)]2(2+) (salen(2-) = N,N'-ethylenebis-(salicylideneiminate)) into a ferromagnetic bimetallic oxalate network affords the hybrid compound [Mn(III)(salen)(H2O)]2[Mn(II)Cr(III)(ox)3]2⋅(CH3OH)⋅(CH3CN)2 (1). This cationic Mn2 cluster templates the growth of crystals formed by an unusual achiral 3D oxalate network. The magnetic properties of this hybrid magnet are compared with those of the analogous compounds [Mn(III)(salen)(H2O)]2[Zn(II)Cr(III)(ox)3]2⋅(CH3OH)⋅(CH3CN)2 (2) and [In(III)(sal2-trien)][Mn(II)Cr(III)(ox)3]⋅(H2O)0.25⋅(CH3OH)0.25⋅(CH3CN)0.25 (3), which are used as reference compounds. In 2 it has been shown that the magnetic isolation of the Mn2 clusters provided by their insertion into a paramagnetic oxalate network of Cr(III) affords a SMM behavior, albeit with blocking temperatures well below 500 mK even for frequencies as high as 160 kHz. In 3 the onset of ferromagnetism in the bimetallic Mn(II) Cr(III) network is observed at Tc = 5 K. Finally, in the hybrid compound 1 the interaction between the two magnetic networks leads to the antiparallel arrangement of their respective magnetizations, that is, to a ferrimagnetic phase. This coupling induces also important changes on the magnetic properties of 1 with respect to those of the reference compounds 2 and 3. In particular, compound 1 shows a large magnetization hysteresis below 1 K, which is in sharp contrast with the near-reversible magnetizations that the SMMs and the oxalate ferromagnetic lattice show under the same conditions.

  11. Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

    PubMed Central

    Guimarães, Maria C; Duarte, Mariene H; Silla, Josué M

    2016-01-01

    Summary An intriguing question in 3D-QSAR lies on which conformation(s) to use when generating molecular descriptors (MD) for correlation with bioactivity values. This is not a simple task because the bioactive conformation in molecule data sets is usually unknown and, therefore, optimized structures in a receptor-free environment are often used to generate the MD´s. In this case, a wrong conformational choice can cause misinterpretation of the QSAR model. The present computational work reports the conformational analysis of the volatile anesthetic isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane) in the gas phase and also in polar and nonpolar implicit and explicit solvents to show that stable minima (ruled by intramolecular interactions) do not necessarily coincide with the bioconformation (ruled by enzyme induced fit). Consequently, a QSAR model based on two-dimensional chemical structures was built and exhibited satisfactory modeling/prediction capability and interpretability, then suggesting that these 2D MD´s can be advantageous over some three-dimensional descriptors. PMID:27340468

  12. Molecular modeling studies of 4,5-dihydro-1H-pyrazolo[4,3-h] quinazoline derivatives as potent CDK2/Cyclin a inhibitors using 3D-QSAR and docking.

    PubMed

    Ai, Yong; Wang, Shao-Teng; Sun, Ping-Hua; Song, Fa-Jun

    2010-09-28

    CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r(2) (cv) values of 0.747 and 0.518 and r(2) values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity.

  13. An alignment independent 3D QSAR study of the antiproliferative activity of 1,2,4,5-tetraoxanes.

    PubMed

    Cvijetić, Ilija N; Zizak, Zeljko P; Stanojković, Tatjana P; Juranić, Zorica D; Terzić, Natasa; Opsenica, Igor M; Opsenica, Dejan M; Juranić, Ivan O; Drakulić, Branko J

    2010-10-01

    An alignment-free 3D QSAR study on antiproliferative activity of the thirty-three 1,2,4,5-tetraoxane derivatives toward two human dedifferentiated cell lines was reported. GRIND methodology, where descriptors are derived from GRID molecular interaction fields (MIF), were used. It was found that pharmacophoric pattern attributed to the most potent derivatives include amido NH of the primary or secondary amide, and the acetoxy fragments at positions 7 and 12 of steroid core which are, along with the tetraoxane ring, common for all studied compounds. Independently, simple multiple regression model obtained by using the whole-molecular properties, confirmed that the hydrophobicity and the H-bond donor properties are the main parameters influencing potency of compounds toward human cervix carcinoma (HeLa) and human malignant melanoma (FemX) cell lines. Corollary, similar structural motifs are found to be important for the potency toward both examined cell lines.

  14. Ames interactive molecular model building system - A 3-D computer modelling system applied to the study of the origin of life

    NASA Technical Reports Server (NTRS)

    Coeckelenbergh, Y.; Macelroy, R. D.; Rein, R.

    1978-01-01

    The investigation of specific interactions among biological molecules must take into consideration the stereochemistry of the structures. Thus, models of the molecules are essential for describing the spatial organization of potentially interacting groups, and estimations of conformation are required for a description of spatial organization. Both the function of visualizing molecules, and that of estimating conformation through calculations of energy, are part of the molecular modeling system described in the present paper. The potential uses of the system in investigating some aspects of the origin of life rest on the assumption that translation of conformation from genetic elements to catalytic elements would have been required for the development of the first replicating systems subject to the process of biological evolution.

  15. A structure-odour relationship study using EVA descriptors and hierarchical clustering.

    PubMed

    Takane, Shin-ya; Mitchell, John B O

    2004-11-21

    Structure-odour relationship analyses using hierarchical clustering were carried out on a diverse dataset of 47 molecules. These molecules were divided into seven odour categories: ambergris, bitter almond, camphoraceous, rose, jasmine, muguet, and musk. The alignment-independent descriptor EVA (EigenVAlue) was used as the molecular descriptor. The results were compared with those of another kind of descriptor, the UNITY 2D fingerprint. The dendrograms obtained with these descriptors were compared with the seven odour categories using the adjusted Rand index. The dendrograms produced by EVA consistently outperformed those from UNITY 2D in reproducing the experimental odour classifications of these 47 molecules.

  16. Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-chromen-2-One Core: Structure-Based and Ligand-Based Derived 3-D QSAR Predictive Models.

    PubMed

    Mladenovic, Milan; Patsilinakos, Alexandros; Pirolli, Adele; Sabatino, Manuela; Ragno, Rino

    2017-03-14

    Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition. Aiming to contribute to the development of drugs with the reversible mechanism of MAO B inhibition only, herein, an extended in silico-in vitro procedure for the selection of novel MAO B inhibitors is demonstrated, including: (1) definition of optimized and validated structure-based (SB) 3-D QSAR models derived from available co-crystallized inhibitor-MAO B complexes; (2) elaboration of structure-activity relationships (SAR) features for either irreversible or reversible MAO B inhibitors to characterize and improve coumarin-based inhibitor activity (Protein Data Bank ID: 2V61) as the most potent reversible lead compound; (3) definition of structure-based (SB) and ligand-based (LB) alignment rules assessments by which virtually any untested potential MAO B inhibitor might be evaluated; (4) predictive ability validation of the best 3-D QSAR model through SB/LB modeling of four coumarin-based external test sets (267 compounds); (5) design and SB/LB alignment of novel coumarin-based scaffolds experimentally validated through synthesis and biological evaluation in vitro. Due to the wide range of molecular diversity within the 3-D QSARs training set and derived features, the selected N probe-derived 3-D QSAR model proves to be a valuable tool for virtual screening (VS) of novel MAO B inhibitors and a platform for design, synthesis and evaluation of novel active structures. Accordingly, six highly active and selective MAO B inhibitors (picomolar to low nanomolar range of activity) were disclosed as a result of rational SB/LB 3-D QSAR design

  17. Analysis of the antioxidant activity of 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid derivatives using quantum-chemistry descriptors and molecular docking.

    PubMed

    Ardjani, Ahmed Taki Eddine; Mekelleche, Sidi Mohamed

    2016-12-01

    In the present work, the molecular structure and the antioxidant activity of 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid (A) and its derivatives (B-E) have been studied at the B3LYP/6-31++G(2d,2p) computational level. The obtained results indicate that the hydrogen atom transfer (HAT mechanism) is thermodynamically more favored in gas phase; whereas, the sequential proton loss-electron transfer (SPLET mechanism) is more preferred in polar solvents. The antioxidant activity of compounds A-E is also analyzed by the calculation of atomic spin densities, chemical hardnesses, dipole moments, and lipophilicity indexes. It turns out that compound E (R = t-Bu) is predicted to be more antioxidant than ascorbic acid and other derivatives A-D in both gas phase and polar solvents. The high antioxidant activity of compound E compared to other derivatives A-D is also rationalized using the molecular docking technique.

  18. Exploring 3D structure of human gonadotropin hormone receptor at antagonist state using homology modeling, molecular dynamic simulation, and cross-docking studies.

    PubMed

    Sakhteman, Amirhossein; Khoddami, Minasadat; Negahdaripour, Manica; Mehdizadeh, Arash; Tatar, Mohsen; Ghasemi, Younes

    2016-09-01

    Human gonadotropin hormone receptor, a G-protein coupled receptor, is the target of many medications used in fertility disorders. Obtaining more structural information about the receptor could be useful in many studies related to drug design. In this study, the structure of human gonadotropin receptor was subjected to homology modeling studies and molecular dynamic simulation within a DPPC lipid bilayer for 100 ns. Several frames were thereafter extracted from simulation trajectories representing the receptor at different states. In order to find a proper model of the receptor at the antagonist state, all frames were subjected to cross-docking studies of some antagonists with known experimental values (Ki). Frame 194 revealed a reasonable correlation between docking calculated energy scores and experimental activity values (|r| = 0.91). The obtained correlation was validated by means of SSLR and showed the presence of no chance correlation for the obtained model. Different structural features reported for the receptor, such as two disulfide bridges and ionic lock between GLU90 and LYS 121 were also investigated in the final model.

  19. Nanoimprint-assisted directed self-assembly of low-molecular weight block copolymers: a route for 3D and multilevel nanostructures

    NASA Astrophysics Data System (ADS)

    Simão, C.; Khunsin, W.; Kehagias, N.; Francone, A.; Zelsmann, M.; Morris, M. A.; Sotomayor Torres, C. M.

    2014-06-01

    Multilevel controllable nanoimprint driven molecular orientation has been obtained in thin films of block copolymer polystyrene-b-polyethylene oxide( PS-b-PEO) by means of solvent vapours assisted nanoimprint lithography (SAIL). The NIL setup using solvent vapours was capable of imprinting nanoscale features over a large area and simultaneously annealing PS-b-PEO thin films. A line pattern stamp was replicated in the BCP film in over a large area with a high resolution registry, and was also observed that the PS-b-PEO film exhibited microphase segregation in the residual layer exhibits a nanodot array from showing hexagonally packed PEO dots in the PS matrix, with a diameter of 20 nm with 40 nm pitch. The order of the hexagonally arranged nanodot lattice seen in the nanodots array was quantified from SEM images using by the opposite partner method from SEM images analysis and compared with to conventionally solvent annealed BCP films, demonstrating an improvement of the ordering of up to 50%. Grazing-incidence small-angle X-ray scattering (GISAXS) study demonstrates the excellent fidelity of the pattern transfer and confirms the periodicity of the BCP in the mesas. In addition, applying the SAIL methodology to BCP thin films in nanopatterned silsequioxane substrates, it was possible to obtain multilevel structures decorated with the BCP microphase segregation. The SAIL technique is a versatile and robust platform to obtain complex high density periodic nanostructures, particularly for second generation block copolymers directed self-assembly.

  20. Classical and quantum aspects of spin interaction in 3 d chains on a C u3N -Cu(110) molecular network

    NASA Astrophysics Data System (ADS)

    Bazhanov, D. I.; Stepanyuk, O. V.; Farberovich, O. V.; Stepanyuk, V. S.

    2016-01-01

    We present a study of the magnetic states and exchange coupling in transition-metal Mn, Fe, and Co atomic chains deposited on a self-corrugated C u3N -Cu(110) molecular network by means of first-principles calculations based on the density functional theory. The various adsorption sites on a bumping area of a self-corrugated C u3N layer are investigated where the atomic chains are formed at the initial stage of nanowire growth. We demonstrate, by calculating the ground-state magnetic configurations, that the exchange coupling, magnetic order, and anisotropies in atomic chains depend sensitively on their chemical composition and adsorption sites on the C u3N network. We find that the exchange interactions in atomic chains could lead to ferromagnetic or antiferromagnetic coupling of atomic spins depending on the position of the chain on the surface. The classical spin dynamics is investigated by means of the kinetic Monte Carlo method based on transition-state theory. Moreover we evaluate the Heisenberg-Dirac-Van Vleck quantum spin Hamiltonian for calculations of the magnetic susceptibility, in order to demonstrate the existence of quantum entanglement in the antiferromagnetic atomic chains at low temperatures.

  1. Generation of a 3D model for human GABA transporter hGAT-1 using molecular modeling and investigation of the binding of GABA.

    PubMed

    Wein, Thomas; Wanner, Klaus T

    2010-01-01

    A three-dimensional model of the human Na(+)/Cl(-)-dependent gamma-aminobutyric acid (GABA) transporter hGAT-1 was developed by homology modeling and refined by subsequent molecular modeling using the crystal structure of a bacterial homologue leucine transporter from Aquifex aeolicus (LeuT(Aa)) as the template. Protein structure quality checks show that the resulting structure is particularly suited for the analysis of the substrate binding pocket and virtual screening experiments. Interactions of GABA and the substrate binding pocket were investigated using docking studies. The difference of 6 out of 13 substrate interacting side chains between hGAT-1 and LeuT(Aa) lead to the different substrate preference which can be explained using our three-dimensional model of hGAT-1. In particular the replacement of serine 256 and isoleucine 359 in LeuT(Aa) with glycine and threonine in hGAT-1 seems to facilitate the selection of GABA as the main substrate by changing the hydrogen bonding pattern in the active site to the amino group of the substrate. For a set of 12 compounds flexible docking experiments were performed using LigandFit in combination with the Jain scoring function. With few exceptions the obtained rank order of potency was in line with experimental data. Thus, the method can be assumed to give at least a rough estimate of the potency of the potential of GABA uptake inhibitors.

  2. 3D Spectroscopy in Astronomy

    NASA Astrophysics Data System (ADS)

    Mediavilla, Evencio; Arribas, Santiago; Roth, Martin; Cepa-Nogué, Jordi; Sánchez, Francisco

    2011-09-01

    Preface; Acknowledgements; 1. Introductory review and technical approaches Martin M. Roth; 2. Observational procedures and data reduction James E. H. Turner; 3. 3D Spectroscopy instrumentation M. A. Bershady; 4. Analysis of 3D data Pierre Ferruit; 5. Science motivation for IFS and galactic studies F. Eisenhauer; 6. Extragalactic studies and future IFS science Luis Colina; 7. Tutorials: how to handle 3D spectroscopy data Sebastian F. Sánchez, Begona García-Lorenzo and Arlette Pécontal-Rousset.

  3. Spherical 3D isotropic wavelets

    NASA Astrophysics Data System (ADS)

    Lanusse, F.; Rassat, A.; Starck, J.-L.

    2012-04-01

    Context. Future cosmological surveys will provide 3D large scale structure maps with large sky coverage, for which a 3D spherical Fourier-Bessel (SFB) analysis in spherical coordinates is natural. Wavelets are particularly well-suited to the analysis and denoising of cosmological data, but a spherical 3D isotropic wavelet transform does not currently exist to analyse spherical 3D data. Aims: The aim of this paper is to present a new formalism for a spherical 3D isotropic wavelet, i.e. one based on the SFB decomposition of a 3D field and accompany the formalism with a public code to perform wavelet transforms. Methods: We describe a new 3D isotropic spherical wavelet decomposition based on the undecimated wavelet transform (UWT) described in Starck et al. (2006). We also present a new fast discrete spherical Fourier-Bessel transform (DSFBT) based on both a discrete Bessel transform and the HEALPIX angular pixelisation scheme. We test the 3D wavelet transform and as a toy-application, apply a denoising algorithm in wavelet space to the Virgo large box cosmological simulations and find we can successfully remove noise without much loss to the large scale structure. Results: We have described a new spherical 3D isotropic wavelet transform, ideally suited to analyse and denoise future 3D spherical cosmological surveys, which uses a novel DSFBT. We illustrate its potential use for denoising using a toy model. All the algorithms presented in this paper are available for download as a public code called MRS3D at http://jstarck.free.fr/mrs3d.html

  4. 3D facial landmark detection under large yaw and expression variations.

    PubMed

    Perakis, Panagiotis; Passalis, Georgios; Theoharis, Theoharis; Kakadiaris, Ioannis A

    2013-07-01

    A 3D landmark detection method for 3D facial scans is presented and thoroughly evaluated. The main contribution of the presented method is the automatic and pose-invariant detection of landmarks on 3D facial scans under large yaw variations (that often result in missing facial data), and its robustness against large facial expressions. Three-dimensional information is exploited by using 3D local shape descriptors to extract candidate landmark points. The shape descriptors include the shape index, a continuous map of principal curvature values of a 3D object's surface, and spin images, local descriptors of the object's 3D point distribution. The candidate landmarks are identified and labeled by matching them with a Facial Landmark Model (FLM) of facial anatomical landmarks. The presented method is extensively evaluated against a variety of 3D facial databases and achieves state-of-the-art accuracy (4.5-6.3 mm mean landmark localization error), considerably outperforming previous methods, even when tested with the most challenging data.

  5. 3D Elevation Program—Virtual USA in 3D

    USGS Publications Warehouse

    Lukas, Vicki; Stoker, J.M.

    2016-04-14

    The U.S. Geological Survey (USGS) 3D Elevation Program (3DEP) uses a laser system called ‘lidar’ (light detection and ranging) to create a virtual reality map of the Nation that is very accurate. 3D maps have many uses with new uses being discovered all the time.  

  6. Assessment of metal-assisted nucleophile activation in the hepatitis delta virus ribozyme from molecular simulation and 3D-RISM

    PubMed Central

    Radak, Brian K.; Lee, Tai-Sung; Harris, Michael E.

    2015-01-01

    The hepatitis delta virus ribozyme is an efficient catalyst of RNA 2′-O-transphosphorylation and has emerged as a key experimental system for identifying and characterizing fundamental features of RNA catalysis. Recent structural and biochemical data have led to a proposed mechanistic model whereby an active site Mg2+ ion facilitates deprotonation of the O2′ nucleophile, and a protonated cytosine residue (C75) acts as an acid to donate a proton to the O5′ leaving group as noted in a previous study. This model assumes that the active site Mg2+ ion forms an inner-sphere coordination with the O2′ nucleophile and a nonbridging oxygen of the scissile phosphate. These contacts, however, are not fully resolved in the crystal structure, and biochemical data are not able to unambiguously exclude other mechanistic models. In order to explore the feasibility of this model, we exhaustively mapped the free energy surfaces with different active site ion occupancies via quantum mechanical/molecular mechanical (QM/MM) simulations. We further incorporate a three-dimensional reference interaction site model for the solvated ion atmosphere that allows these calculations to consider not only the rate associated with the chemical steps, but also the probability of observing the system in the presumed active state with the Mg2+ ion bound. The QM/MM results predict that a pathway involving metal-assisted nucleophile activation is feasible based on the rate-controlling transition state barrier departing from the presumed metal-bound active state. However, QM/MM results for a similar pathway in the absence of Mg2+ are not consistent with experimental data, suggesting that a structural model in which the crystallographically determined Mg2+ is simply replaced with Na+ is likely incorrect. It should be emphasized, however, that these results hinge upon the assumption of the validity of the presumed Mg2+-bound starting state, which has not yet been definitively verified experimentally

  7. Fourier descriptor features for acoustic landmine detection

    NASA Astrophysics Data System (ADS)

    Keller, James M.; Cheng, Zhanqi; Gader, Paul D.; Hocaoglu, Ali K.

    2002-08-01

    Signatures of buried landmines are often difficult to separate from those of clutter objects. Often, shape information is not directly obtainable from the sensors used for landmine detection. The Acoustic Sensing Technology (AST), which uses a Laser Doppler Vibrometer (LDV) that measures the spatial pattern of particle velocity amplitude of the ground surface in a variety of frequency bands, offers a unique look at subsurface phenomena. It directly records shape related information. Generally, after preprocessing the frequency band images in a downward looking LDV system, landmines have fairly regular shapes (roughly circular) over a range of frequencies while clutter tends to exhibit irregular shapes different from those of landmines. Therefore, shape description has the potential to be used in discriminating mines from clutter. Normalized Fourier Descriptors (NFD) are shape parameters independent of size, angular orientation, position, and contour starting conditions. In this paper, the stack of 2D frequency images from the LDV system are preprocessed by a linear combination of order statistics (LOS) filter, thresholding, and 2D and 3D connected labeling. Contours are extracted form the connected components and aggregated to produce evenly spaced boundary points. Two types of Normalized Fourier Descriptors are computed from the outlines. Using images obtained from a standard data collection site, these features are analyzed for their ability to discriminate landmines from background and clutter such as wood and stones. From a standard feature selection procedure, it was found that a very small number of features are required to effectively separate landmines from background and clutter using simple pattern recognition algorithms. Details of the experiments are included.

  8. 3D point cloud registration based on the assistant camera and Harris-SIFT

    NASA Astrophysics Data System (ADS)

    Zhang, Yue; Yu, HongYang

    2016-07-01

    3D(Three-Dimensional) point cloud registration technology is the hot topic in the field of 3D reconstruction, but most of the registration method is not real-time and ineffective. This paper proposes a point cloud registration method of 3D reconstruction based on Harris-SIFT and assistant camera. The assistant camera is used to pinpoint mobile 3D reconstruction device, The feature points of images are detected by using Harris operator, the main orientation for each feature point is calculated, and lastly, the feature point descriptors are generated after rotating the coordinates of the descriptors relative to the feature points' main orientations. Experimental results of demonstrate the effectiveness of the proposed method.

  9. 3D World Building System

    ScienceCinema

    None

    2016-07-12

    This video provides an overview of the Sandia National Laboratories developed 3-D World Model Building capability that provides users with an immersive, texture rich 3-D model of their environment in minutes using a laptop and color and depth camera.

  10. 3D Buckligami: Digital Matter

    NASA Astrophysics Data System (ADS)

    van Hecke, Martin; de Reus, Koen; Florijn, Bastiaan; Coulais, Corentin

    2014-03-01

    We present a class of elastic structures which exhibit collective buckling in 3D, and create these by a 3D printing/moulding technique. Our structures consist of cubic lattice of anisotropic unit cells, and we show that their mechanical properties are programmable via the orientation of these unit cells.

  11. 3D World Building System

    SciTech Connect

    2013-10-30

    This video provides an overview of the Sandia National Laboratories developed 3-D World Model Building capability that provides users with an immersive, texture rich 3-D model of their environment in minutes using a laptop and color and depth camera.

  12. LLNL-Earth3D

    SciTech Connect

    2013-10-01

    Earth3D is a computer code designed to allow fast calculation of seismic rays and travel times through a 3D model of the Earth. LLNL is using this for earthquake location and global tomography efforts and such codes are of great interest to the Earth Science community.

  13. Market study: 3-D eyetracker

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A market study of a proposed version of a 3-D eyetracker for initial use at NASA's Ames Research Center was made. The commercialization potential of a simplified, less expensive 3-D eyetracker was ascertained. Primary focus on present and potential users of eyetrackers, as well as present and potential manufacturers has provided an effective means of analyzing the prospects for commercialization.

  14. A Generally Applicable Computer Algorithm Based on the Group Additivity Method for the Calculation of Seven Molecular Descriptors: Heat of Combustion, LogPO/W, LogS, Refractivity, Polarizability, Toxicity and LogBB of Organic Compounds; Scope and Limits of Applicability.

    PubMed

    Naef, Rudolf

    2015-10-07

    A generally applicable computer algorithm for the calculation of the seven molecular descriptors heat of combustion, logPoctanol/water, logS (water solubility), molar refractivity, molecular polarizability, aqueous toxicity (protozoan growth inhibition) and logBB (log (cblood/cbrain)) is presented. The method, an extendable form of the group-additivity method, is based on the complete break-down of the molecules into their constituting atoms and their immediate neighbourhood. The contribution of the resulting atom groups to the descriptor values is calculated using the Gauss-Seidel fitting method, based on experimental data gathered from literature. The plausibility of the method was tested for each descriptor by means of a k-fold cross-validation procedure demonstrating good to excellent predictive power for the former six descriptors and low reliability of logBB predictions. The goodness of fit (Q²) and the standard deviation of the 10-fold cross-validation calculation was >0.9999 and 25.2 kJ/mol, respectively, (based on N = 1965 test compounds) for the heat of combustion, 0.9451 and 0.51 (N = 2640) for logP, 0.8838 and 0.74 (N = 1419) for logS, 0.9987 and 0.74 (N = 4045) for the molar refractivity, 0.9897 and 0.77 (N = 308) for the molecular polarizability, 0.8404 and 0.42 (N = 810) for the toxicity and 0.4709 and 0.53 (N = 383) for logBB. The latter descriptor revealing a very low Q² for the test molecules (R² was 0.7068 and standard deviation 0.38 for N = 413 training molecules) is included as an example to show the limits of the group-additivity method. An eighth molecular descriptor, the heat of formation, was indirectly calculated from the heat of combustion data and correlated with published experimental heat of formation data with a correlation coefficient R² of 0.9974 (N = 2031).

  15. Robust Reconstruction and Generalized Dual Hahn Moments Invariants Extraction for 3D Images

    NASA Astrophysics Data System (ADS)

    Mesbah, Abderrahim; Zouhri, Amal; El Mallahi, Mostafa; Zenkouar, Khalid; Qjidaa, Hassan

    2017-03-01

    In this paper, we introduce a new set of 3D weighed dual Hahn moments which are orthogonal on a non-uniform lattice and their polynomials are numerically stable to scale, consequent, producing a set of weighted orthonormal polynomials. The dual Hahn is the general case of Tchebichef and Krawtchouk, and the orthogonality of dual Hahn moments eliminates the numerical approximations. The computational aspects and symmetry property of 3D weighed dual Hahn moments are discussed in details. To solve their inability to invariability of large 3D images, which cause to overflow issues, a generalized version of these moments noted 3D generalized weighed dual Hahn moment invariants are presented where whose as linear combination of regular geometric moments. For 3D pattern recognition, a generalized expression of 3D weighted dual Hahn moment invariants, under translation, scaling and rotation transformations, have been proposed where a new set of 3D-GWDHMIs have been provided. In experimental studies, the local and global capability of free and noisy 3D image reconstruction of the 3D-WDHMs has been compared with other orthogonal moments such as 3D Tchebichef and 3D Krawtchouk moments using Princeton Shape Benchmark database. On pattern recognition using the 3D-GWDHMIs like 3D object descriptors, the experimental results confirm that the proposed algorithm is more robust than other orthogonal moments for pattern classification of 3D images with and without noise.

  16. Euro3D Science Conference

    NASA Astrophysics Data System (ADS)

    Walsh, J. R.

    2004-02-01

    The Euro3D RTN is an EU funded Research Training Network to foster the exploitation of 3D spectroscopy in Europe. 3D spectroscopy is a general term for spectroscopy of an area of the sky and derives its name from its two spatial + one spectral dimensions. There are an increasing number of instruments which use integral field devices to achieve spectroscopy of an area of the sky, either using lens arrays, optical fibres or image slicers, to pack spectra of multiple pixels on the sky (``spaxels'') onto a 2D detector. On account of the large volume of data and the special methods required to reduce and analyse 3D data, there are only a few centres of expertise and these are mostly involved with instrument developments. There is a perceived lack of expertise in 3D spectroscopy spread though the astronomical community and its use in the armoury of the observational astronomer is viewed as being highly specialised. For precisely this reason the Euro3D RTN was proposed to train young researchers in this area and develop user tools to widen the experience with this particular type of data in Europe. The Euro3D RTN is coordinated by Martin M. Roth (Astrophysikalisches Institut Potsdam) and has been running since July 2002. The first Euro3D science conference was held in Cambridge, UK from 22 to 23 May 2003. The main emphasis of the conference was, in keeping with the RTN, to expose the work of the young post-docs who are funded by the RTN. In addition the team members from the eleven European institutes involved in Euro3D also presented instrumental and observational developments. The conference was organized by Andy Bunker and held at the Institute of Astronomy. There were over thirty participants and 26 talks covered the whole range of application of 3D techniques. The science ranged from Galactic planetary nebulae and globular clusters to kinematics of nearby galaxies out to objects at high redshift. Several talks were devoted to reporting recent observations with newly

  17. 3D vision system assessment

    NASA Astrophysics Data System (ADS)

    Pezzaniti, J. Larry; Edmondson, Richard; Vaden, Justin; Hyatt, Bryan; Chenault, David B.; Kingston, David; Geulen, Vanilynmae; Newell, Scott; Pettijohn, Brad

    2009-02-01

    In this paper, we report on the development of a 3D vision system consisting of a flat panel stereoscopic display and auto-converging stereo camera and an assessment of the system's use for robotic driving, manipulation, and surveillance operations. The 3D vision system was integrated onto a Talon Robot and Operator Control Unit (OCU) such that direct comparisons of the performance of a number of test subjects using 2D and 3D vision systems were possible. A number of representative scenarios were developed to determine which tasks benefited most from the added depth perception and to understand when the 3D vision system hindered understanding of the scene. Two tests were conducted at Fort Leonard Wood, MO with noncommissioned officers ranked Staff Sergeant and Sergeant First Class. The scenarios; the test planning, approach and protocols; the data analysis; and the resulting performance assessment of the 3D vision system are reported.

  18. 3D printing in dentistry.

    PubMed

    Dawood, A; Marti Marti, B; Sauret-Jackson, V; Darwood, A

    2015-12-01

    3D printing has been hailed as a disruptive technology which will change manufacturing. Used in aerospace, defence, art and design, 3D printing is becoming a subject of great interest in surgery. The technology has a particular resonance with dentistry, and with advances in 3D imaging and modelling technologies such as cone beam computed tomography and intraoral scanning, and with the relatively long history of the use of CAD CAM technologies in dentistry, it will become of increasing importance. Uses of 3D printing include the production of drill guides for dental implants, the production of physical models for prosthodontics, orthodontics and surgery, the manufacture of dental, craniomaxillofacial and orthopaedic implants, and the fabrication of copings and frameworks for implant and dental restorations. This paper reviews the types of 3D printing technologies available and their various applications in dentistry and in maxillofacial surgery.

  19. PLOT3D user's manual

    NASA Technical Reports Server (NTRS)

    Walatka, Pamela P.; Buning, Pieter G.; Pierce, Larry; Elson, Patricia A.

    1990-01-01

    PLOT3D is a computer graphics program designed to visualize the grids and solutions of computational fluid dynamics. Seventy-four functions are available. Versions are available for many systems. PLOT3D can handle multiple grids with a million or more grid points, and can produce varieties of model renderings, such as wireframe or flat shaded. Output from PLOT3D can be used in animation programs. The first part of this manual is a tutorial that takes the reader, keystroke by keystroke, through a PLOT3D session. The second part of the manual contains reference chapters, including the helpfile, data file formats, advice on changing PLOT3D, and sample command files.

  20. Extra dimensions: 3D in PDF documentation

    SciTech Connect

    Graf, Norman A.

    2011-01-11

    Experimental science is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standard Universal 3D (U3D) file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. By providing support for scripting and animation, temporal data can also be easily distributed to a wide, non-technical audience. We discuss how the field of radiation imaging could benefit from incorporating full 3D information about not only the detectors, but also the results of the experimental analyses, in its electronic publications. In this article, we present examples drawn from high-energy physics, mathematics and molecular biology which take advantage of this functionality. Furthermore, we demonstrate how 3D detector elements can be documented, using either CAD drawings or other sources such as GEANT visualizations as input.

  1. Extra dimensions: 3D in PDF documentation

    DOE PAGES

    Graf, Norman A.

    2011-01-11

    Experimental science is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standard Universalmore » 3D (U3D) file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. By providing support for scripting and animation, temporal data can also be easily distributed to a wide, non-technical audience. We discuss how the field of radiation imaging could benefit from incorporating full 3D information about not only the detectors, but also the results of the experimental analyses, in its electronic publications. In this article, we present examples drawn from high-energy physics, mathematics and molecular biology which take advantage of this functionality. Furthermore, we demonstrate how 3D detector elements can be documented, using either CAD drawings or other sources such as GEANT visualizations as input.« less

  2. Shape-based classification of 3D facial data to support 22q11.2DS craniofacial research.

    PubMed

    Wilamowska, Katarzyna; Wu, Jia; Heike, Carrie; Shapiro, Linda

    2012-06-01

    3D imaging systems are used to construct high-resolution meshes of patient's heads that can be analyzed by computer algorithms. Our work starts with such 3D head meshes and produces both global and local descriptors of 3D shape. Since these descriptors are numeric feature vectors, they can be used in both classification and quantification of various different abnormalities. In this paper, we define these descriptors, describe our methodology for constructing them from 3D head meshes, and show through a set of classification experiments involving cases and controls for a genetic disorder called 22q11.2 deletion syndrome that they are suitable for use in craniofacial research studies. The main contributions of this work include: automatic generation of novel global and local data representations, robust automatic placement of anthropometric landmarks, generation of local descriptors for nasal and oral facial features from landmarks, use of local descriptors for predicting various local facial features, and use of global features for 22q11.2DS classification, showing their potential use as descriptors in craniofacial research.

  3. Improved nucleic acid descriptors for siRNA efficacy prediction

    PubMed Central

    Sciabola, Simone; Cao, Qing; Orozco, Modesto; Faustino, Ignacio; Stanton, Robert V.

    2013-01-01

    Although considerable progress has been made recently in understanding how gene silencing is mediated by the RNAi pathway, the rational design of effective sequences is still a challenging task. In this article, we demonstrate that including three-dimensional descriptors improved the discrimination between active and inactive small interfering RNAs (siRNAs) in a statistical model. Five descriptor types were used: (i) nucleotide position along the siRNA sequence, (ii) nucleotide composition in terms of presence/absence of specific combinations of di- and trinucleotides, (iii) nucleotide interactions by means of a modified auto- and cross-covariance function, (iv) nucleotide thermodynamic stability derived by the nearest neighbor model representation and (v) nucleic acid structure flexibility. The duplex flexibility descriptors are derived from extended molecular dynamics simulations, which are able to describe the sequence-dependent elastic properties of RNA duplexes, even for non-standard oligonucleotides. The matrix of descriptors was analysed using three statistical packages in R (partial least squares, random forest, and support vector machine), and the most predictive model was implemented in a modeling tool we have made publicly available through SourceForge. Our implementation of new RNA descriptors coupled with appropriate statistical algorithms resulted in improved model performance for the selection of siRNA candidates when compared with publicly available siRNA prediction tools and previously published test sets. Additional validation studies based on in-house RNA interference projects confirmed the robustness of the scoring procedure in prospective studies. PMID:23241392

  4. PLOT3D/AMES, APOLLO UNIX VERSION USING GMR3D (WITHOUT TURB3D)

    NASA Technical Reports Server (NTRS)

    Buning, P.

    1994-01-01

    PLOT3D is an interactive graphics program designed to help scientists visualize computational fluid dynamics (CFD) grids and solutions. Today, supercomputers and CFD algorithms can provide scientists with simulations of such highly complex phenomena that obtaining an understanding of the simulations has become a major problem. Tools which help the scientist visualize the simulations can be of tremendous aid. PLOT3D/AMES offers more functions and features, and has been adapted for more types of computers than any other CFD graphics program. Version 3.6b+ is supported for five computers and graphic libraries. Using PLOT3D, CFD physicists can view their computational models from any angle, observing the physics of problems and the quality of solutions. As an aid in designing aircraft, for example, PLOT3D's interactive computer graphics can show vortices, temperature, reverse flow, pressure, and dozens of other characteristics of air flow during flight. As critical areas become obvious, they can easily be studied more closely using a finer grid. PLOT3D is part of a computational fluid dynamics software cycle. First, a program such as 3DGRAPE (ARC-12620) helps the scientist generate computational grids to model an object and its surrounding space. Once the grids have been designed and parameters such as the angle of attack, Mach number, and Reynolds number have been specified, a "flow-solver" program such as INS3D (ARC-11794 or COS-10019) solves the system of equations governing fluid flow, usually on a supercomputer. Grids sometimes have as many as two million points, and the "flow-solver" produces a solution file which contains density, x- y- and z-momentum, and stagnation energy for each grid point. With such a solution file and a grid file containing up to 50 grids as input, PLOT3D can calculate and graphically display any one of 74 functions, including shock waves, surface pressure, velocity vectors, and particle traces. PLOT3D's 74 functions are organized into

  5. PLOT3D/AMES, APOLLO UNIX VERSION USING GMR3D (WITH TURB3D)

    NASA Technical Reports Server (NTRS)

    Buning, P.

    1994-01-01

    PLOT3D is an interactive graphics program designed to help scientists visualize computational fluid dynamics (CFD) grids and solutions. Today, supercomputers and CFD algorithms can provide scientists with simulations of such highly complex phenomena that obtaining an understanding of the simulations has become a major problem. Tools which help the scientist visualize the simulations can be of tremendous aid. PLOT3D/AMES offers more functions and features, and has been adapted for more types of computers than any other CFD graphics program. Version 3.6b+ is supported for five computers and graphic libraries. Using PLOT3D, CFD physicists can view their computational models from any angle, observing the physics of problems and the quality of solutions. As an aid in designing aircraft, for example, PLOT3D's interactive computer graphics can show vortices, temperature, reverse flow, pressure, and dozens of other characteristics of air flow during flight. As critical areas become obvious, they can easily be studied more closely using a finer grid. PLOT3D is part of a computational fluid dynamics software cycle. First, a program such as 3DGRAPE (ARC-12620) helps the scientist generate computational grids to model an object and its surrounding space. Once the grids have been designed and parameters such as the angle of attack, Mach number, and Reynolds number have been specified, a "flow-solver" program such as INS3D (ARC-11794 or COS-10019) solves the system of equations governing fluid flow, usually on a supercomputer. Grids sometimes have as many as two million points, and the "flow-solver" produces a solution file which contains density, x- y- and z-momentum, and stagnation energy for each grid point. With such a solution file and a grid file containing up to 50 grids as input, PLOT3D can calculate and graphically display any one of 74 functions, including shock waves, surface pressure, velocity vectors, and particle traces. PLOT3D's 74 functions are organized into

  6. CheS-Mapper - Chemical Space Mapping and Visualization in 3D

    PubMed Central

    2012-01-01

    Analyzing chemical datasets is a challenging task for scientific researchers in the field of chemoinformatics. It is important, yet difficult to understand the relationship between the structure of chemical compounds, their physico-chemical properties, and biological or toxic effects. To that respect, visualization tools can help to better comprehend the underlying correlations. Our recently developed 3D molecular viewer CheS-Mapper (Chemical Space Mapper) divides large datasets into clusters of similar compounds and consequently arranges them in 3D space, such that their spatial proximity reflects their similarity. The user can indirectly determine similarity, by selecting which features to employ in the process. The tool can use and calculate different kind of features, like structural fragments as well as quantitative chemical descriptors. These features can be highlighted within CheS-Mapper, which aids the chemist to better understand patterns and regularities and relate the observations to established scientific knowledge. As a final function, the tool can also be used to select and export specific subsets of a given dataset for further analysis. PMID:22424447

  7. How Does the Methodology of 3D Structure Preparation Influence the Quality of pKa Prediction?

    PubMed

    Geidl, Stanislav; Svobodová Vařeková, Radka; Bendová, Veronika; Petrusek, Lukáš; Ionescu, Crina-Maria; Jurka, Zdeněk; Abagyan, Ruben; Koča, Jaroslav

    2015-06-22

    The acid dissociation constant is an important molecular property, and it can be successfully predicted by Quantitative Structure-Property Relationship (QSPR) models, even for in silico designed molecules. We analyzed how the methodology of in silico 3D structure preparation influences the quality of QSPR models. Specifically, we evaluated and compared QSPR models based on six different 3D structure sources (DTP NCI, Pubchem, Balloon, Frog2, OpenBabel, and RDKit) combined with four different types of optimization. These analyses were performed for three classes of molecules (phenols, carboxylic acids, anilines), and the QSPR model descriptors were quantum mechanical (QM) and empirical partial atomic charges. Specifically, we developed 516 QSPR models and afterward systematically analyzed the influence of the 3D structure source and other factors on their quality. Our results confirmed that QSPR models based on partial atomic charges are able to predict pKa with high accuracy. We also confirmed that ab initio and semiempirical QM charges provide very accurate QSPR models and using empirical charges based on electronegativity equalization is also acceptable, as well as advantageous, because their calculation is very fast. On the other hand, Gasteiger-Marsili empirical charges are not applicable for pKa prediction. We later found that QSPR models for some classes of molecules (carboxylic acids) are less accurate. In this context, we compared the influence of different 3D structure sources. We found that an appropriate selection of 3D structure source and optimization method is essential for the successful QSPR modeling of pKa. Specifically, the 3D structures from the DTP NCI and Pubchem databases performed the best, as they provided very accurate QSPR models for all the tested molecular classes and charge calculation approaches, and they do not require optimization. Also, Frog2 performed very well. Other 3D structure sources can also be used but are not so robust, and

  8. Unassisted 3D camera calibration

    NASA Astrophysics Data System (ADS)

    Atanassov, Kalin; Ramachandra, Vikas; Nash, James; Goma, Sergio R.

    2012-03-01

    With the rapid growth of 3D technology, 3D image capture has become a critical part of the 3D feature set on mobile phones. 3D image quality is affected by the scene geometry as well as on-the-device processing. An automatic 3D system usually assumes known camera poses accomplished by factory calibration using a special chart. In real life settings, pose parameters estimated by factory calibration can be negatively impacted by movements of the lens barrel due to shaking, focusing, or camera drop. If any of these factors displaces the optical axes of either or both cameras, vertical disparity might exceed the maximum tolerable margin and the 3D user may experience eye strain or headaches. To make 3D capture more practical, one needs to consider unassisted (on arbitrary scenes) calibration. In this paper, we propose an algorithm that relies on detection and matching of keypoints between left and right images. Frames containing erroneous matches, along with frames with insufficiently rich keypoint constellations, are detected and discarded. Roll, pitch yaw , and scale differences between left and right frames are then estimated. The algorithm performance is evaluated in terms of the remaining vertical disparity as compared to the maximum tolerable vertical disparity.

  9. Combined experimental (FT-IR, UV-visible spectra, NMR) and theoretical studies on the molecular structure, vibrational spectra, HOMO, LUMO, MESP surfaces, reactivity descriptor and molecular docking of Phomarin

    NASA Astrophysics Data System (ADS)

    Kumar, Abhishek; Srivastava, Ambrish Kumar; Gangwar, Shashi; Misra, Neeraj; Mondal, Avijit; Brahmachari, Goutam

    2015-09-01

    Phomarin is an important natural product belonging to anthraquinone series of compounds. The equilibrium geometry of phomarin has been determined and analyzed at DFT method employing B3LYP/6-311++G(d,p) level of computation. The reactivity of molecule using various descriptors such as Fukui functions, local softness, electrophilicity, electronegativity, Hardness, HOMO-LUMO gap are calculated and discussed. The infrared and UV-vis spectra of phomarin are calculated and compared with the experimentally observed ones. Moreover, 1H and 13C NMR spectra have been calculated by using the gauge independent atomic orbital method. We also notice that phomarin shows remarkable biological activities against malaria parasite. The study suggests further investigation on phomarin for their pharmacological importance.

  10. 3D Scan Systems Integration

    DTIC Science & Technology

    2007-11-02

    AGENCY USE ONLY (Leave Blank) 2. REPORT DATE 5 Feb 98 4. TITLE AND SUBTITLE 3D Scan Systems Integration REPORT TYPE AND DATES COVERED...2-89) Prescribed by ANSI Std. Z39-1 298-102 [ EDO QUALITY W3PECTEDI DLA-ARN Final Report for US Defense Logistics Agency on DDFG-T2/P3: 3D...SCAN SYSTEMS INTEGRATION Contract Number SPO100-95-D-1014 Contractor Ohio University Delivery Order # 0001 Delivery Order Title 3D Scan Systems

  11. A 2D-QSAR and Grid-Independent Molecular Descriptor (GRIND) Analysis of Quinoline-Type Inhibitors of Akt2: Exploration of the Binding Mode in the Pleckstrin Homology (PH) Domain

    PubMed Central

    Akhtar, Noreen; Jabeen, Ishrat

    2016-01-01

    Protein kinase B-β (PKBβ/Akt2) is a serine/threonine-specific protein kinase that has emerged as one of the most important regulators of cell growth, differentiation, and division. Upregulation of Akt2 in various human carcinomas, including ovarian, breast, and pancreatic, is a well-known tumorigenesis phenomenon. Early on, the concept of the simultaneous administration of anticancer drugs with inhibitors of Akt2 was advocated to overcome cell proliferation in the chemotherapeutic treatment of cancer. However, clinical studies have not lived up to the high expectations, and several phase II and phase III clinical studies have been terminated prematurely because of severe side effects related to the non-selective isomeric inhibition of Akt2. The notion that the sequence identity of pleckstrin homology (PH) domains within Akt-isoforms is less than 30% might indicate the possibility of the development of selective antagonists against the Akt2 PH domain. Therefore, in this study, various in silico tools were utilized to explore the hypothesis that quinoline-type inhibitors bind in the Akt2 PH domain. A Grid-Independent Molecular Descriptor (GRIND) analysis indicated that two hydrogen bond acceptors, two hydrogen bond donors and one hydrophobic feature at a certain distance from each other were important for the selective inhibition of Akt2. Our docking results delineated the importance of Lys30 as an anchor point for mapping the distances of important amino acid residues in the binding pocket, including Lys14, Glu17, Arg25, Asn53, Asn54 and Arg86. The binding regions identified complement the GRIND-based pharmacophoric features. PMID:28036396

  12. 3D polymer scaffold arrays.

    PubMed

    Simon, Carl G; Yang, Yanyin; Dorsey, Shauna M; Ramalingam, Murugan; Chatterjee, Kaushik

    2011-01-01

    We have developed a combinatorial platform for fabricating tissue scaffold arrays that can be used for screening cell-material interactions. Traditional research involves preparing samples one at a time for characterization and testing. Combinatorial and high-throughput (CHT) methods lower the cost of research by reducing the amount of time and material required for experiments by combining many samples into miniaturized specimens. In order to help accelerate biomaterials research, many new CHT methods have been developed for screening cell-material interactions where materials are presented to cells as a 2D film or surface. However, biomaterials are frequently used to fabricate 3D scaffolds, cells exist in vivo in a 3D environment and cells cultured in a 3D environment in vitro typically behave more physiologically than those cultured on a 2D surface. Thus, we have developed a platform for fabricating tissue scaffold libraries where biomaterials can be presented to cells in a 3D format.

  13. Autofocus for 3D imaging

    NASA Astrophysics Data System (ADS)

    Lee-Elkin, Forest

    2008-04-01

    Three dimensional (3D) autofocus remains a significant challenge for the development of practical 3D multipass radar imaging. The current 2D radar autofocus methods are not readily extendable across sensor passes. We propose a general framework that allows a class of data adaptive solutions for 3D auto-focus across passes with minimal constraints on the scene contents. The key enabling assumption is that portions of the scene are sparse in elevation which reduces the number of free variables and results in a system that is simultaneously solved for scatterer heights and autofocus parameters. The proposed method extends 2-pass interferometric synthetic aperture radar (IFSAR) methods to an arbitrary number of passes allowing the consideration of scattering from multiple height locations. A specific case from the proposed autofocus framework is solved and demonstrates autofocus and coherent multipass 3D estimation across the 8 passes of the "Gotcha Volumetric SAR Data Set" X-Band radar data.

  14. Reproducibility of 3D chromatin configuration reconstructions

    PubMed Central

    Segal, Mark R.; Xiong, Hao; Capurso, Daniel; Vazquez, Mariel; Arsuaga, Javier

    2014-01-01

    It is widely recognized that the three-dimensional (3D) architecture of eukaryotic chromatin plays an important role in processes such as gene regulation and cancer-driving gene fusions. Observing or inferring this 3D structure at even modest resolutions had been problematic, since genomes are highly condensed and traditional assays are coarse. However, recently devised high-throughput molecular techniques have changed this situation. Notably, the development of a suite of chromatin conformation capture (CCC) assays has enabled elicitation of contacts—spatially close chromosomal loci—which have provided insights into chromatin architecture. Most analysis of CCC data has focused on the contact level, with less effort directed toward obtaining 3D reconstructions and evaluating the accuracy and reproducibility thereof. While questions of accuracy must be addressed experimentally, questions of reproducibility can be addressed statistically—the purpose of this paper. We use a constrained optimization technique to reconstruct chromatin configurations for a number of closely related yeast datasets and assess reproducibility using four metrics that measure the distance between 3D configurations. The first of these, Procrustes fitting, measures configuration closeness after applying reflection, rotation, translation, and scaling-based alignment of the structures. The others base comparisons on the within-configuration inter-point distance matrix. Inferential results for these metrics rely on suitable permutation approaches. Results indicate that distance matrix-based approaches are preferable to Procrustes analysis, not because of the metrics per se but rather on account of the ability to customize permutation schemes to handle within-chromosome contiguity. It has recently been emphasized that the use of constrained optimization approaches to 3D architecture reconstruction are prone to being trapped in local minima. Our methods of reproducibility assessment provide a

  15. Combinatorial 3D Mechanical Metamaterials

    NASA Astrophysics Data System (ADS)

    Coulais, Corentin; Teomy, Eial; de Reus, Koen; Shokef, Yair; van Hecke, Martin

    2015-03-01

    We present a class of elastic structures which exhibit 3D-folding motion. Our structures consist of cubic lattices of anisotropic unit cells that can be tiled in a complex combinatorial fashion. We design and 3d-print this complex ordered mechanism, in which we combine elastic hinges and defects to tailor the mechanics of the material. Finally, we use this large design space to encode smart functionalities such as surface patterning and multistability.

  16. 3D Imaging by Mass Spectrometry: A New Frontier

    PubMed Central

    Seeley, Erin H.; Caprioli, Richard M.

    2012-01-01

    Summary Imaging mass spectrometry can generate three-dimensional volumes showing molecular distributions in an entire organ or animal through registration and stacking of serial tissue sections. Here we review the current state of 3D imaging mass spectrometry as well as provide insights and perspectives on the process of generating 3D mass spectral data along with a discussion of the process necessary to generate a 3D image volume. PMID:22276611

  17. 3D ear identification based on sparse representation.

    PubMed

    Zhang, Lin; Ding, Zhixuan; Li, Hongyu; Shen, Ying

    2014-01-01

    Biometrics based personal authentication is an effective way for automatically recognizing, with a high confidence, a person's identity. Recently, 3D ear shape has attracted tremendous interests in research field due to its richness of feature and ease of acquisition. However, the existing ICP (Iterative Closet Point)-based 3D ear matching methods prevalent in the literature are not quite efficient to cope with the one-to-many identification case. In this paper, we aim to fill this gap by proposing a novel effective fully automatic 3D ear identification system. We at first propose an accurate and efficient template-based ear detection method. By utilizing such a method, the extracted ear regions are represented in a common canonical coordinate system determined by the ear contour template, which facilitates much the following stages of feature extraction and classification. For each extracted 3D ear, a feature vector is generated as its representation by making use of a PCA-based local feature descriptor. At the stage of classification, we resort to the sparse representation based classification approach, which actually solves an l1-minimization problem. To the best of our knowledge, this is the first work introducing the sparse representation framework into the field of 3D ear identification. Extensive experiments conducted on a benchmark dataset corroborate the effectiveness and efficiency of the proposed approach. The associated Matlab source code and the evaluation results have been made publicly online available at http://sse.tongji.edu.cn/linzhang/ear/srcear/srcear.htm.

  18. Molecular docking and 3D-QSAR study on 4-(1H-indazol-4-yl) phenylamino and aminopyrazolopyridine urea derivatives as kinase insert domain receptor (KDR) inhibitors.

    PubMed

    Wu, Xiaoyun; Wu, Shuguang; Chen, Wen-Hua

    2012-03-01

    Vascular endothselial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2 or kinase insert domain receptor (KDR) have been identified as new promising targets for the design of novel anticancer agents. It is reported that 4-(1H-indazol-4-yl)phenylamino and aminopyrazolopyridine urea derivatives exhibit potent inhibitory activities toward KDR. To investigate how their chemical structures relate to the inhibitory activities and to identify the key structural elements that are required in the rational design of potential drug candidates of this class, molecular docking simulations and three-dimensional quantitative structure-activity relationship (3D-QSAR) methods were performed on 78 4-(1H-indazol-4-yl)phenylamino and aminopyrazolopyridine urea derivatives as KDR inhibitors. Surflex-dock was used to determine the probable binding conformations of all the compounds at the active site of KDR. As a result, multiple hydrophobic and hydrogen-bonding interactions were found to be two predominant factors that may be used to modulate the inhibitory activities. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) 3D-QSAR models were developed based on the docking conformations. The CoMFA model produced statistically significant results with the cross-validated correlation coefficient q(2) of 0.504 and the non-cross-validated correlation coefficient r(2) of 0.913. The best CoMSIA model was obtained from the combination of steric, electrostatic and hydrophobic fields. Its q(2) and r(2) being 0.595 and 0.947, respectively, indicated that it had higher predictive ability than the CoMFA model. The predictive abilities of the two models were further validated by 14 test compounds, giving the predicted correction coefficients r (pred) (2) of 0.727 for CoMFA and 0.624 for CoMSIA, respectively. In addition, the CoMFA and CoMSIA models were used to guide the design of a series of new inhibitors of this class with

  19. Modeling the 3D structure of wheat subtilisin/chymotrypsin inhibitor (WSCI). Probing the reactive site with two susceptible proteinases by time-course analysis and molecular dynamics simulations.

    PubMed

    Facchiano, Angelo M; Costantini, Susan; Di Maro, Antimo; Panichi, Daniela; Chambery, Angela; Parente, Augusto; Di Gennaro, Simone; Poerio, Elia

    2006-07-01

    Comparative modeling and time-course hydrolysis experiments have been applied to investigate two enzyme-inhibitor complexes formed between the wheat subtilisin-chymotrypsin inhibitor (WSCI) and two susceptible proteinases. WSCI represents the first case of a wheat protein inhibitor active against animal chymotrypsins and bacterial subtilisins. The model was created using as template structure that of the CI-2A inhibitor from barley (PDB code: 2CI2), which shares 87% sequence identity with WSCI. Under these conditions of high similarity, the comparative modeling approach can be successfully applied. We predicted the WSCI 3D model and used it to investigate enzyme-inhibitor complex systems. Experimental observations indicated that chymotrypsin, but not subtilisin, in addition to cleavage at the primary reactive site Met48-Glu49, is able to hydrolyze a second peptide bond between Phe58 and Val59. Here, we report on cleavage of the peptide bond at the inhibitor's reactive site (Met48-Glu49) determined using time-course hydrolysis experiments; the same event was investigated for both subtilisin/WSCI and chymotrypsin/WSCI complexes using molecular dynamics simulations. The molecular details of the initial inhibitor-enzyme interactions, as well as of the changes observed during the simulations, allow us to speculate on the different fates of the two WSCI-proteinase complexes.

  20. Studies of tricyclic piperazine/piperidine furnished molecules as novel integrin αvβ3/αIIbβ3 dual antagonists using 3D-QSAR and molecular docking.

    PubMed

    Yan, Yulian; Li, Yan; Zhang, Shuwei; Ai, Chunzhi

    2011-02-01

    The development of injectable integrin α(v)β(3)/α(IIb)β(3) dual antagonists attracts much attention of research for treating of acute ischemic diseases in recent years. In this work, based on a dataset composed of 102 tricyclic piperazine/piperidine furnished dual α(v)β(3) and α(IIb)β(3) antagonists, a variety of in silico modeling approaches including the comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), and molecular docking were applied to reveal the requisite 3D structural features impacting the biological activities. Our statistical results show that the ligand-based 3D-QSAR models for both the α(v)β(3) and α(IIb)β(3) studies exhibited satisfactory internal and external predictability, i.e., for the CoMFA models, results of Q(2)=0.48, R(ncv)(2)=0.87, R(pred)(2)=0.71 for α(v)β(3) and Q(2)=0.50, R(ncv)(2)=0.85, R(pred)(2)=0.72 for α(IIb)β(3) analysis were obtained, and for the CoMSIA ones, the outcomes of Q(2)=0.55, R(ncv)(2)=0.90, R(pred)(2)=0.72 for α(v)β(3) and Q(2)=0.52, R(ncv)(2)=0.88, R(pred)(2)=0.74 for α(IIb)β(3) were achieved respectively. In addition, through a comparison between 3D-QSAR contour maps and docking results, it is revealed that that the most crucial interactions occurring between the tricyclic piperazine/piperidine derivatives and α(v)β(3)/α(IIb)β(3) receptor ligand binding pocket are H-bonding, and the key amino acids impacting the interactions are Arg214, Asn215, Ser123, and Lys253 for α(v)β(3), but Arg214, Asn215, Ser123 and Tyr190 for α(IIb)β(3) receptors, respectively. Halogen-containing groups at position 15 and 16, benzene sulfonamide substituent at position 23, and the replacement of piperazine with 4-aminopiperidine of ring B may increase the α(v)β(3)/α(IIb)β(3) antagonistic activity. The potencies for antagonists to inhibit isolated α(v)β(3) and α(IIb)β(3) are linear correlated, indicating that similar interaction mechanisms may exist for the series

  1. 3D-shape-based retrieval within the MPEG-7 framework

    NASA Astrophysics Data System (ADS)

    Zaharia, Titus; Preteux, Francoise J.

    2001-05-01

    Because of the continuous development of multimedia technologies, virtual worlds and augmented reality, 3D contents become a common feature of the today information systems. Hence, standardizing tools for content-based indexing of visual data is a key issue for computer vision related applications. Within the framework of the future MPEG-7 standard, tools for intelligent content-based access to 3D information, targeting applications such as search and retrieval and browsing of 3D model databases, have been recently considered and evaluated. In this paper, we present the 3D Shape Spectrum Descriptor (3D SSD), recently adopted within the current MPEG-7 Committee Draft (CD). The proposed descriptor aims at providing an intrinsic shape description of a 3D mesh and is defined as the distribution of the shape index over the entire mesh. The shape index is a local geometric attribute of a 3D surface, expressed as the angular coordinate of a polar representation of the principal curvature vector. Experimental results have been carried out upon the MPEG-7 3D model database consisting of about 1300 meshes in VRML 2.0 format. Objective retrieval results, based upon the definition of a ground truth subset, are reported in terms of Bull Eye Percentage (BEP) score.

  2. Modeling and analysis of 3-D elongated shapes with applications to long bone morphometry

    SciTech Connect

    Burdin, V.; Roux, C.; Lefevre, C.; Stindel, E.

    1996-02-01

    This paper presents a geometric model to be used as a framework for the description and analysis of three-dimensional (3-D) elongated shapes. Elongated shapes can be decomposed into two different parts: a 3-D curve (the central axis) and a 3-D surface (the straight surface). The central axis is described in terms of curvature and torsion. A novel concept of torsion image is introduced which allows the user to study the torsion of some relevant 3-D structures such as the medulla of long bones, without computing the third derivative. The description of the straight surface is based on an ordered set of Fourier Descriptors (FD`s), each set representing a 2-D slice of the structure. These descriptors possess completeness, continuity, and stability properties, and some geometrical invariancies. A polar diagram is built which contains the anatomical information of the straight surface and can be used as a tool for the analysis and discrimination of 3-D structures. A technique for the reconstruction of the 3-D surface from the model`s two components is presented. Various applications to the analysis of long bone structures, such as the ulna and radius, are derived from the model, namely, data compression, comparison of 3-D shapes, segmentation into 3-D primitives, and torsion and curvature analysis. The relevance of the method to morphometry and to clinical applications is discussed.

  3. From 3D view to 3D print

    NASA Astrophysics Data System (ADS)

    Dima, M.; Farisato, G.; Bergomi, M.; Viotto, V.; Magrin, D.; Greggio, D.; Farinato, J.; Marafatto, L.; Ragazzoni, R.; Piazza, D.

    2014-08-01

    In the last few years 3D printing is getting more and more popular and used in many fields going from manufacturing to industrial design, architecture, medical support and aerospace. 3D printing is an evolution of bi-dimensional printing, which allows to obtain a solid object from a 3D model, realized with a 3D modelling software. The final product is obtained using an additive process, in which successive layers of material are laid down one over the other. A 3D printer allows to realize, in a simple way, very complex shapes, which would be quite difficult to be produced with dedicated conventional facilities. Thanks to the fact that the 3D printing is obtained superposing one layer to the others, it doesn't need any particular work flow and it is sufficient to simply draw the model and send it to print. Many different kinds of 3D printers exist based on the technology and material used for layer deposition. A common material used by the toner is ABS plastics, which is a light and rigid thermoplastic polymer, whose peculiar mechanical properties make it diffusely used in several fields, like pipes production and cars interiors manufacturing. I used this technology to create a 1:1 scale model of the telescope which is the hardware core of the space small mission CHEOPS (CHaracterising ExOPlanets Satellite) by ESA, which aims to characterize EXOplanets via transits observations. The telescope has a Ritchey-Chrétien configuration with a 30cm aperture and the launch is foreseen in 2017. In this paper, I present the different phases for the realization of such a model, focusing onto pros and cons of this kind of technology. For example, because of the finite printable volume (10×10×12 inches in the x, y and z directions respectively), it has been necessary to split the largest parts of the instrument in smaller components to be then reassembled and post-processed. A further issue is the resolution of the printed material, which is expressed in terms of layers

  4. YouDash3D: exploring stereoscopic 3D gaming for 3D movie theaters

    NASA Astrophysics Data System (ADS)

    Schild, Jonas; Seele, Sven; Masuch, Maic

    2012-03-01

    Along with the success of the digitally revived stereoscopic cinema, events beyond 3D movies become attractive for movie theater operators, i.e. interactive 3D games. In this paper, we present a case that explores possible challenges and solutions for interactive 3D games to be played by a movie theater audience. We analyze the setting and showcase current issues related to lighting and interaction. Our second focus is to provide gameplay mechanics that make special use of stereoscopy, especially depth-based game design. Based on these results, we present YouDash3D, a game prototype that explores public stereoscopic gameplay in a reduced kiosk setup. It features live 3D HD video stream of a professional stereo camera rig rendered in a real-time game scene. We use the effect to place the stereoscopic effigies of players into the digital game. The game showcases how stereoscopic vision can provide for a novel depth-based game mechanic. Projected trigger zones and distributed clusters of the audience video allow for easy adaptation to larger audiences and 3D movie theater gaming.

  5. Speaking Volumes About 3-D

    NASA Technical Reports Server (NTRS)

    2002-01-01

    In 1999, Genex submitted a proposal to Stennis Space Center for a volumetric 3-D display technique that would provide multiple users with a 360-degree perspective to simultaneously view and analyze 3-D data. The futuristic capabilities of the VolumeViewer(R) have offered tremendous benefits to commercial users in the fields of medicine and surgery, air traffic control, pilot training and education, computer-aided design/computer-aided manufacturing, and military/battlefield management. The technology has also helped NASA to better analyze and assess the various data collected by its satellite and spacecraft sensors. Genex capitalized on its success with Stennis by introducing two separate products to the commercial market that incorporate key elements of the 3-D display technology designed under an SBIR contract. The company Rainbow 3D(R) imaging camera is a novel, three-dimensional surface profile measurement system that can obtain a full-frame 3-D image in less than 1 second. The third product is the 360-degree OmniEye(R) video system. Ideal for intrusion detection, surveillance, and situation management, this unique camera system offers a continuous, panoramic view of a scene in real time.

  6. To What Degree Does Handling Concrete Molecular Models Promote the Ability to Translate and Coordinate between 2D and 3D Molecular Structure Representations? A Case Study with Algerian Students

    ERIC Educational Resources Information Center

    Mohamed-Salah, Boukhechem; Alain, Dumon

    2016-01-01

    This study aims to assess whether the handling of concrete ball-and-stick molecular models promotes translation between diagrammatic representations and a concrete model (or vice versa) and the coordination of the different types of structural representations of a given molecular structure. Forty-one Algerian undergraduate students were requested…

  7. Crouzon syndrome associated with acanthosis nigricans: prenatal 2D and 3D ultrasound findings and postnatal 3D CT findings

    PubMed Central

    Nørgaard, Pernille; Hagen, Casper Petri; Hove, Hanne; Dunø, Morten; Nissen, Kamilla Rothe; Kreiborg, Sven; Jørgensen, Finn Stener

    2012-01-01

    Crouzon syndrome with acanthosis nigricans (CAN) is a very rare condition with an approximate prevalence of 1 per 1 million newborns. We add the first report on prenatal 2D and 3D ultrasound findings in CAN. In addition we present the postnatal 3D CT findings. The diagnosis was confirmed by molecular testing. PMID:23986840

  8. Petal, terrain & airbags - 3D

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Portions of the lander's deflated airbags and a petal are at the lower area of this image, taken in stereo by the Imager for Mars Pathfinder (IMP) on Sol 3. 3D glasses are necessary to identify surface detail. The metallic object at lower right is part of the lander's low-gain antenna. This image is part of a 3D 'monster

    Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  9. 3D Computations and Experiments

    SciTech Connect

    Couch, R; Faux, D; Goto, D; Nikkel, D

    2004-04-05

    This project consists of two activities. Task A, Simulations and Measurements, combines all the material model development and associated numerical work with the materials-oriented experimental activities. The goal of this effort is to provide an improved understanding of dynamic material properties and to provide accurate numerical representations of those properties for use in analysis codes. Task B, ALE3D Development, involves general development activities in the ALE3D code with the focus of improving simulation capabilities for problems of mutual interest to DoD and DOE. Emphasis is on problems involving multi-phase flow, blast loading of structures and system safety/vulnerability studies.

  10. 3-D QSAutogrid/R: an alternative procedure to build 3-D QSAR models. Methodologies and applications.

    PubMed

    Ballante, Flavio; Ragno, Rino

    2012-06-25

    Since it first appeared in 1988 3-D QSAR has proved its potential in the field of drug design and activity prediction. Although thousands of citations now exist in 3-D QSAR, its development was rather slow with the majority of new 3-D QSAR applications just extensions of CoMFA. An alternative way to build 3-D QSAR models, based on an evolution of software, has been named 3-D QSAutogrid/R and has been developed to use only software freely available to academics. 3-D QSAutogrid/R covers all the main features of CoMFA and GRID/GOLPE with implementation by multiprobe/multiregion variable selection (MPGRS) that improves the simplification of interpretation of the 3-D QSAR map. The methodology is based on the integration of the molecular interaction fields as calculated by AutoGrid and the R statistical environment that can be easily coupled with many free graphical molecular interfaces such as UCSF-Chimera, AutoDock Tools, JMol, and others. The description of each R package is reported in detail, and, to assess its validity, 3-D QSAutogrid/R has been applied to three molecular data sets of which either CoMFA or GRID/GOLPE models were reported in order to compare the results. 3-D QSAutogrid/R has been used as the core engine to prepare more that 240 3-D QSAR models forming the very first 3-D QSAR server ( www.3d-qsar.com ) with its code freely available through R-Cran distribution.

  11. Generalized Hough transform based time invariant action recognition with 3D pose information

    NASA Astrophysics Data System (ADS)

    Muench, David; Huebner, Wolfgang; Arens, Michael

    2014-10-01

    Human action recognition has emerged as an important field in the computer vision community due to its large number of applications such as automatic video surveillance, content based video-search and human robot interaction. In order to cope with the challenges that this large variety of applications present, recent research has focused more on developing classifiers able to detect several actions in more natural and unconstrained video sequences. The invariance discrimination tradeoff in action recognition has been addressed by utilizing a Generalized Hough Transform. As a basis for action representation we transform 3D poses into a robust feature space, referred to as pose descriptors. For each action class a one-dimensional temporal voting space is constructed. Votes are generated from associating pose descriptors with their position in time relative to the end of an action sequence. Training data consists of manually segmented action sequences. In the detection phase valid human 3D poses are assumed as input, e.g. originating from 3D sensors or monocular pose reconstruction methods. The human 3D poses are normalized to gain view-independence and transformed into (i) relative limb-angle space to ensure independence of non-adjacent joints or (ii) geometric features. In (i) an action descriptor consists of the relative angles between limbs and their temporal derivatives. In (ii) the action descriptor consists of different geometric features. In order to circumvent the problem of time-warping we propose to use a codebook of prototypical 3D poses which is generated from sample sequences of 3D motion capture data. This idea is in accordance with the concept of equivalence classes in action space. Results of the codebook method are presented using the Kinect sensor and the CMU Motion Capture Database.

  12. Neutral dioxovanadium(V) complexes of biomimetic hydrazones ONO donor ligands of bioinorganic and medicinal relevance: Synthesis via air oxidation of bis(acetylaceto-nato)oxovanadium(IV), characterization, biological activity and 3D molecular modeling

    NASA Astrophysics Data System (ADS)

    Maurya, R. C.; Rajput, S.

    2007-05-01

    The interaction of bis(acetylacetonato)oxovanadium(IV), [VO(acac) 2] with biomimetic hydrazone ONO donor ligands HL in 1:1 mole ratio [where, HL = N-(4'-benzoylidene-3'-methyl-1'-phenyl-2'-pyrazolin-5'-one)-isonicotinic acid hydrazide (bmphp-inH, I), N-(4'-butyrylidene-3'-methyl-1'-phenyl-2'-pyrazolin-5'-one)-isonicotinic acid hydrazide (bumphp-inH, II), N-(4'-acetylidene-3'-methyl-1'-phenyl-2'-pyrazolin-5'-one)-isonicotinic acid hydrazide (amphp-inH, III), N-(3'-methyl-1'-phenyl-4'-propionylidene-2'-pyrazolin-5'-one)-isonicotinic acid hydrazide (mphpp-inH, IV) and N-(4'- iso-butyrylidene-3'-methyl-1'-phenyl-2'-pyrazolin-5'-one)-isonicotinic acid hydrazide ( iso-bumphp-inH, V)] in a mixed solvent (ethanol-methanol, 1:10) via aerial oxidation for 2-3 days yield dioxovanadium(V) complexes of composition [VO 2(L)(H 2O)] · H 2O. The compounds so obtained were characterized on the basis of elemental analyses, thermogravimetry, vanadium determination, IR, Electronic, 51V NMR, 1H NMR and mass spectral studies. The 3D molecular modeling and analysis for bond lengths and bond angles have also been carried out for one of the representative compounds, [VO 2(ampph-in)(H 2O)] ( 3).

  13. Molecular evolution of VP3, VP1, 3C(pro) and 3D(pol) coding regions in coxsackievirus group A type 24 variant isolates from acute hemorrhagic conjunctivitis in 2011 in Okinawa, Japan.

    PubMed

    Nidaira, Minoru; Kuba, Yumani; Saitoh, Mika; Taira, Katsuya; Maeshiro, Noriyuki; Mahoe, Yoko; Kyan, Hisako; Takara, Taketoshi; Okano, Sho; Kudaka, Jun; Yoshida, Hiromu; Oishi, Kazunori; Kimura, Hirokazu

    2014-04-01

    A large acute hemorrhagic conjunctivitis (AHC) outbreak occurred in 2011 in Okinawa Prefecture in Japan. Ten strains of coxsackievirus group A type 24 variant (CA24v) were isolated from patients with AHC and full sequence analysis of the VP3, VP1, 3C(pro) and 3D(pol) coding regions performed. To assess time-scale evolution, phylogenetic analysis was performed using the Bayesian Markov chain Monte Carlo method. In addition, similarity plots were constructed and pairwise distance (p-distance) and positive pressure analyses performed. A phylogenetic tree based on the VP1 coding region showed that the present strains belong to genotype 4 (G4). In addition, the present strains could have divided in about 2010 from the same lineages detected in other countries such as China, India and Australia. The mean rates of molecular evolution of four coding regions were estimated at about 6.15 to 7.86 × 10(-3) substitutions/site/year. Similarity plot analyses suggested that nucleotide similarities between the present strains and a prototype strain (EH24/70 strain) were 0.77-0.94. The p-distance of the present strains was relatively short (<0.01). Only one positive selected site (L25H) was identified in the VP1 protein. These findings suggest that the present CA24v strains causing AHC are genetically related to other AHC strains with rapid evolution and emerged in around 2010.

  14. 3D-QSAR studies and molecular docking on [5-(4-amino-1 H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors

    NASA Astrophysics Data System (ADS)

    Lan, Ping; Xie, Mei-Qi; Yao, Yue-Mei; Chen, Wan-Na; Chen, Wei-Min

    2010-12-01

    Fructose-1,6-biphophatase has been regarded as a novel therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). 3D-QSAR and docking studies were performed on a series of [5-(4-amino-1 H-benzoimidazol-2-yl)-furan-2-yl]-phosphonic acid derivatives as fructose-1,6-biphophatase inhibitors. The CoMFA and CoMSIA models using thirty-seven molecules in the training set gave r cv 2 values of 0.614 and 0.598, r 2 values of 0.950 and 0.928, respectively. The external validation indicated that our CoMFA and CoMSIA models possessed high predictive powers with r 0 2 values of 0.994 and 0.994, r m 2 values of 0.751 and 0.690, respectively. Molecular docking studies revealed that a phosphonic group was essential for binding to the receptor, and some key features were also identified. A set of forty new analogues were designed by utilizing the results revealed in the present study, and were predicted with significantly improved potencies in the developed models. The findings can be quite useful to aid the designing of new fructose-1,6-biphophatase inhibitors with improved biological response.

  15. The World of 3-D.

    ERIC Educational Resources Information Center

    Mayshark, Robin K.

    1991-01-01

    Students explore three-dimensional properties by creating red and green wall decorations related to Christmas. Students examine why images seem to vibrate when red and green pieces are small and close together. Instructions to conduct the activity and construct 3-D glasses are given. (MDH)

  16. 3D Printing: Exploring Capabilities

    ERIC Educational Resources Information Center

    Samuels, Kyle; Flowers, Jim

    2015-01-01

    As 3D printers become more affordable, schools are using them in increasing numbers. They fit well with the emphasis on product design in technology and engineering education, allowing students to create high-fidelity physical models to see and test different iterations in their product designs. They may also help students to "think in three…

  17. SNL3dFace

    SciTech Connect

    Russ, Trina; Koch, Mark; Koudelka, Melissa; Peters, Ralph; Little, Charles; Boehnen, Chris; Peters, Tanya

    2007-07-20

    This software distribution contains MATLAB and C++ code to enable identity verification using 3D images that may or may not contain a texture component. The code is organized to support system performance testing and system capability demonstration through the proper configuration of the available user interface. Using specific algorithm parameters the face recognition system has been demonstrated to achieve a 96.6% verification rate (Pd) at 0.001 false alarm rate. The system computes robust facial features of a 3D normalized face using Principal Component Analysis (PCA) and Fisher Linear Discriminant Analysis (FLDA). A 3D normalized face is obtained by alighning each face, represented by a set of XYZ coordinated, to a scaled reference face using the Iterative Closest Point (ICP) algorithm. The scaled reference face is then deformed to the input face using an iterative framework with parameters that control the deformed surface regulation an rate of deformation. A variety of options are available to control the information that is encoded by the PCA. Such options include the XYZ coordinates, the difference of each XYZ coordinates from the reference, the Z coordinate, the intensity/texture values, etc. In addition to PCA/FLDA feature projection this software supports feature matching to obtain similarity matrices for performance analysis. In addition, this software supports visualization of the STL, MRD, 2D normalized, and PCA synthetic representations in a 3D environment.

  18. Making Inexpensive 3-D Models

    ERIC Educational Resources Information Center

    Manos, Harry

    2016-01-01

    Visual aids are important to student learning, and they help make the teacher's job easier. Keeping with the "TPT" theme of "The Art, Craft, and Science of Physics Teaching," the purpose of this article is to show how teachers, lacking equipment and funds, can construct a durable 3-D model reference frame and a model gravity…

  19. 3D Printed Molecules and Extended Solid Models for Teaching Symmetry and Point Groups

    ERIC Educational Resources Information Center

    Scalfani, Vincent F.; Vaid, Thomas P.

    2014-01-01

    Tangible models help students and researchers visualize chemical structures in three dimensions (3D). 3D printing offers a unique and straightforward approach to fabricate plastic 3D models of molecules and extended solids. In this article, we prepared a series of digital 3D design files of molecular structures that will be useful for teaching…

  20. Local functional descriptors for surface comparison based binding prediction

    PubMed Central

    2012-01-01

    Background Molecular recognition in proteins occurs due to appropriate arrangements of physical, chemical, and geometric properties of an atomic surface. Similar surface regions should create similar binding interfaces. Effective methods for comparing surface regions can be used in identifying similar regions, and to predict interactions without regard to the underlying structural scaffold that creates the surface. Results We present a new descriptor for protein functional surfaces and algorithms for using these descriptors to compare protein surface regions to identify ligand binding interfaces. Our approach uses descriptors of local regions of the surface, and assembles collections of matches to compare larger regions. Our approach uses a variety of physical, chemical, and geometric properties, adaptively weighting these properties as appropriate for different regions of the interface. Our approach builds a classifier based on a training corpus of examples of binding sites of the target ligand. The constructed classifiers can be applied to a query protein providing a probability for each position on the protein that the position is part of a binding interface. We demonstrate the effectiveness of the approach on a number of benchmarks, demonstrating performance that is comparable to the state-of-the-art, with an approach with more generality than these prior methods. Conclusions Local functional descriptors offer a new method for protein surface comparison that is sufficiently flexible to serve in a variety of applications. PMID:23176080

  1. Bringing macromolecular machinery to life using 3D animation.

    PubMed

    Iwasa, Janet H

    2015-04-01

    Over the past decade, there has been a rapid rise in the use of three-dimensional (3D) animation to depict molecular and cellular processes. Much of the growth in molecular animation has been in the educational arena, but increasingly, 3D animation software is finding its way into research laboratories. In this review, I will discuss a number of ways in which 3d animation software can play a valuable role in visualizing and communicating macromolecular structures and dynamics. I will also consider the challenges of using animation tools within the research sphere.

  2. TACO3D. 3-D Finite Element Heat Transfer Code

    SciTech Connect

    Mason, W.E.

    1992-03-04

    TACO3D is a three-dimensional, finite-element program for heat transfer analysis. An extension of the two-dimensional TACO program, it can perform linear and nonlinear analyses and can be used to solve either transient or steady-state problems. The program accepts time-dependent or temperature-dependent material properties, and materials may be isotropic or orthotropic. A variety of time-dependent and temperature-dependent boundary conditions and loadings are available including temperature, flux, convection, and radiation boundary conditions and internal heat generation. Additional specialized features treat enclosure radiation, bulk nodes, and master/slave internal surface conditions (e.g., contact resistance). Data input via a free-field format is provided. A user subprogram feature allows for any type of functional representation of any independent variable. A profile (bandwidth) minimization option is available. The code is limited to implicit time integration for transient solutions. TACO3D has no general mesh generation capability. Rows of evenly-spaced nodes and rows of sequential elements may be generated, but the program relies on separate mesh generators for complex zoning. TACO3D does not have the ability to calculate view factors internally. Graphical representation of data in the form of time history and spatial plots is provided through links to the POSTACO and GRAPE postprocessor codes.

  3. Forensic 3D scene reconstruction

    NASA Astrophysics Data System (ADS)

    Little, Charles Q.; Small, Daniel E.; Peters, Ralph R.; Rigdon, J. B.

    2000-05-01

    Traditionally law enforcement agencies have relied on basic measurement and imaging tools, such as tape measures and cameras, in recording a crime scene. A disadvantage of these methods is that they are slow and cumbersome. The development of a portable system that can rapidly record a crime scene with current camera imaging, 3D geometric surface maps, and contribute quantitative measurements such as accurate relative positioning of crime scene objects, would be an asset to law enforcement agents in collecting and recording significant forensic data. The purpose of this project is to develop a fieldable prototype of a fast, accurate, 3D measurement and imaging system that would support law enforcement agents to quickly document and accurately record a crime scene.

  4. 3D Printed Robotic Hand

    NASA Technical Reports Server (NTRS)

    Pizarro, Yaritzmar Rosario; Schuler, Jason M.; Lippitt, Thomas C.

    2013-01-01

    Dexterous robotic hands are changing the way robots and humans interact and use common tools. Unfortunately, the complexity of the joints and actuations drive up the manufacturing cost. Some cutting edge and commercially available rapid prototyping machines now have the ability to print multiple materials and even combine these materials in the same job. A 3D model of a robotic hand was designed using Creo Parametric 2.0. Combining "hard" and "soft" materials, the model was printed on the Object Connex350 3D printer with the purpose of resembling as much as possible the human appearance and mobility of a real hand while needing no assembly. After printing the prototype, strings where installed as actuators to test mobility. Based on printing materials, the manufacturing cost of the hand was $167, significantly lower than other robotic hands without the actuators since they have more complex assembly processes.

  5. Comparing swimsuits in 3D.

    PubMed

    van Geer, Erik; Molenbroek, Johan; Schreven, Sander; deVoogd-Claessen, Lenneke; Toussaint, Huib

    2012-01-01

    In competitive swimming, suits have become more important. These suits influence friction, pressure and wave drag. Friction drag is related to the surface properties whereas both pressure and wave drag are greatly influenced by body shape. To find a relationship between the body shape and the drag, the anthropometry of several world class female swimmers wearing different suits was accurately defined using a 3D scanner and traditional measuring methods. The 3D scans delivered more detailed information about the body shape. On the same day the swimmers did performance tests in the water with the tested suits. Afterwards the result of the performance tests and the differences found in body shape was analyzed to determine the deformation caused by a swimsuit and its effect on the swimming performance. Although the amount of data is limited because of the few test subjects, there is an indication that the deformation of the body influences the swimming performance.

  6. Forensic 3D Scene Reconstruction

    SciTech Connect

    LITTLE,CHARLES Q.; PETERS,RALPH R.; RIGDON,J. BRIAN; SMALL,DANIEL E.

    1999-10-12

    Traditionally law enforcement agencies have relied on basic measurement and imaging tools, such as tape measures and cameras, in recording a crime scene. A disadvantage of these methods is that they are slow and cumbersome. The development of a portable system that can rapidly record a crime scene with current camera imaging, 3D geometric surface maps, and contribute quantitative measurements such as accurate relative positioning of crime scene objects, would be an asset to law enforcement agents in collecting and recording significant forensic data. The purpose of this project is to develop a feasible prototype of a fast, accurate, 3D measurement and imaging system that would support law enforcement agents to quickly document and accurately record a crime scene.

  7. [Real time 3D echocardiography

    NASA Technical Reports Server (NTRS)

    Bauer, F.; Shiota, T.; Thomas, J. D.

    2001-01-01

    Three-dimensional representation of the heart is an old concern. Usually, 3D reconstruction of the cardiac mass is made by successive acquisition of 2D sections, the spatial localisation and orientation of which require complex guiding systems. More recently, the concept of volumetric acquisition has been introduced. A matricial emitter-receiver probe complex with parallel data processing provides instantaneous of a pyramidal 64 degrees x 64 degrees volume. The image is restituted in real time and is composed of 3 planes (planes B and C) which can be displaced in all spatial directions at any time during acquisition. The flexibility of this system of acquisition allows volume and mass measurement with greater accuracy and reproducibility, limiting inter-observer variability. Free navigation of the planes of investigation allows reconstruction for qualitative and quantitative analysis of valvular heart disease and other pathologies. Although real time 3D echocardiography is ready for clinical usage, some improvements are still necessary to improve its conviviality. Then real time 3D echocardiography could be the essential tool for understanding, diagnosis and management of patients.

  8. Harmonic filters for 3D multichannel data: rotation invariant detection of mitoses in colorectal cancer.

    PubMed

    Schlachter, Matthias; Reisert, Marco; Herz, Corinna; Schlürmann, Fabienne; Lassmann, Silke; Werner, Martin; Burkhardt, Hans; Ronneberger, Olaf

    2010-08-01

    In this paper, we present a novel approach for a trainable rotation invariant detection of complex structures in 3D microscopic multichannel data using a nonlinear filter approach. The basic idea of our approach is to compute local features in a window around each 3D position and map these features by means of a nonlinear mapping onto new local harmonic descriptors of the local window. These local harmonic descriptors are then combined in a linear way to form the output of the filter. The optimal combination of the computed local harmonic descriptors is determined in previous training step, and allows the filter to be adapted to an arbitrary structure depending on the problem at hand. Our approach is not limited to scalar-valued images and can also be used for vector-valued (multichannel) images such as gradient vector flow fields. We present realizations of a scalar-valued and a vector-valued multichannel filter. Our proposed algorithm was quantitatively evaluated on colorectal cancer cell lines (cells grown under controlled conditions), on which we successfully detected complex 3D mitotic structures. For a qualitative evaluation we tested our algorithms on human 3D tissue samples of colorectal cancer. We compare our results with a steerable filter approach as well as a morphology-based approach.

  9. The assess facility descriptor module

    SciTech Connect

    Jordan, S.E.; Winblad, A.; Key, B.; Walker, S.; Renis, T.; Saleh, R.

    1989-01-01

    The Facility Descriptor (Facility) module is part of the Analytic System and Software for Evaluating Safeguards and Security (ASSESS). Facility is the foundational software application in the ASSESS system for modelling a nuclear facility's safeguards and security system to determine the effectiveness against theft of special nuclear material. The Facility module provides the tools for an analyst to define a complete description of a facility's physical protection system which can then be used by other ASSESS software modules to determine vulnerability to a spectrum of insider and outsider threats. The analyst can enter a comprehensive description of the protection system layout including all secured areas, target locations, and detailed safeguards specifications. An extensive safeguard component catalog provides the reference data for calculating delay and detection performance. Multiple target locations within the same physical area may be specified, and the facility may be defined for two different operational states such as dayshift and nightshift. 6 refs., 5 figs.

  10. GPU-Accelerated Denoising in 3D (GD3D)

    SciTech Connect

    2013-10-01

    The raw computational power GPU Accelerators enables fast denoising of 3D MR images using bilateral filtering, anisotropic diffusion, and non-local means. This software addresses two facets of this promising application: what tuning is necessary to achieve optimal performance on a modern GPU? And what parameters yield the best denoising results in practice? To answer the first question, the software performs an autotuning step to empirically determine optimal memory blocking on the GPU. To answer the second, it performs a sweep of algorithm parameters to determine the combination that best reduces the mean squared error relative to a noiseless reference image.

  11. Applications of 3D printing in cardiovascular diseases.

    PubMed

    Giannopoulos, Andreas A; Mitsouras, Dimitris; Yoo, Shi-Joon; Liu, Peter P; Chatzizisis, Yiannis S; Rybicki, Frank J

    2016-12-01

    3D-printed models fabricated from CT, MRI, or echocardiography data provide the advantage of haptic feedback, direct manipulation, and enhanced understanding of cardiovascular anatomy and underlying pathologies. Reported applications of cardiovascular 3D printing span from diagnostic assistance and optimization of management algorithms in complex cardiovascular diseases, to planning and simulating surgical and interventional procedures. The technology has been used in practically the entire range of structural, valvular, and congenital heart diseases, and the added-value of 3D printing is established. Patient-specific implants and custom-made devices can be designed, produced, and tested, thus opening new horizons in personalized patient care and cardiovascular research. Physicians and trainees can better elucidate anatomical abnormalities with the use of 3D-printed models, and communication with patients is markedly improved. Cardiovascular 3D bioprinting and molecular 3D printing, although currently not translated into clinical practice, hold revolutionary potential. 3D printing is expected to have a broad influence in cardiovascular care, and will prove pivotal for the future generation of cardiovascular imagers and care providers. In this Review, we summarize the cardiovascular 3D printing workflow, from image acquisition to the generation of a hand-held model, and discuss the cardiovascular applications and the current status and future perspectives of cardiovascular 3D printing.

  12. Magmatic Systems in 3-D

    NASA Astrophysics Data System (ADS)

    Kent, G. M.; Harding, A. J.; Babcock, J. M.; Orcutt, J. A.; Bazin, S.; Singh, S.; Detrick, R. S.; Canales, J. P.; Carbotte, S. M.; Diebold, J.

    2002-12-01

    Multichannel seismic (MCS) images of crustal magma chambers are ideal targets for advanced visualization techniques. In the mid-ocean ridge environment, reflections originating at the melt-lens are well separated from other reflection boundaries, such as the seafloor, layer 2A and Moho, which enables the effective use of transparency filters. 3-D visualization of seismic reflectivity falls into two broad categories: volume and surface rendering. Volumetric-based visualization is an extremely powerful approach for the rapid exploration of very dense 3-D datasets. These 3-D datasets are divided into volume elements or voxels, which are individually color coded depending on the assigned datum value; the user can define an opacity filter to reject plotting certain voxels. This transparency allows the user to peer into the data volume, enabling an easy identification of patterns or relationships that might have geologic merit. Multiple image volumes can be co-registered to look at correlations between two different data types (e.g., amplitude variation with offsets studies), in a manner analogous to draping attributes onto a surface. In contrast, surface visualization of seismic reflectivity usually involves producing "fence" diagrams of 2-D seismic profiles that are complemented with seafloor topography, along with point class data, draped lines and vectors (e.g. fault scarps, earthquake locations and plate-motions). The overlying seafloor can be made partially transparent or see-through, enabling 3-D correlations between seafloor structure and seismic reflectivity. Exploration of 3-D datasets requires additional thought when constructing and manipulating these complex objects. As numbers of visual objects grow in a particular scene, there is a tendency to mask overlapping objects; this clutter can be managed through the effective use of total or partial transparency (i.e., alpha-channel). In this way, the co-variation between different datasets can be investigated

  13. The unique deep sea—land connection: interactive 3D visualization and molecular phylogeny of Bathyhedyle boucheti n. sp. (Bathyhedylidae n. fam.)—the first panpulmonate slug from bathyal zones

    PubMed Central

    Jörger, Katharina M.; Lodde-Bensch, Eva; Schrödl, Michael

    2016-01-01

    The deep sea comprises vast unexplored areas and is expected to conceal significant undescribed invertebrate species diversity. Deep waters may act as a refuge for many relictual groups, including elusive and enigmatic higher taxa, but the evolutionary pathways by which colonization of the deep sea has occurred have scarcely been investigated. Sister group relationships between shallow water and deep sea taxa have been documented in several invertebrate groups, but are unknown between amphibious/terrestrial and deep-sea species. Here we describe in full and interactive 3D morphoanatomical detail the new sea slug species Bathyhedyle boucheti n. sp., dredged from the continental slope off Mozambique. Molecular and morphological analyses reveal that it represents a novel heterobranch gastropod lineage which we establish as the new family Bathyhedylidae. The family is robustly supported as sister to the recently discovered panpulmonate acochlidian family Aitengidae, which comprises amphibious species living along the sea shore as well as fully terrestrial species. This is the first marine-epibenthic representative among hedylopsacean Acochlidiida, the first record of an acochlidian from deep waters and the first documented panpulmonate deep-sea slug. Considering a marine mesopsammic ancestor, the external morphological features of Bathyhedyle n. gen. may be interpreted as independent adaptations to a benthic life style in the deep sea, including the large body size, broad foot and propodial tentacles. Alternatively, the common ancestor of Bathyhedylidae and Aitengidae may have been a macroscopic amphibious or even terrestrial species. We hypothesize that oophagy in the common ancestor of Aitengidae and Bathyhedylidae might explain the impressive ecological and evolutionary flexibility in habitat choice in the Acochlidiida. PMID:27957391

  14. The unique deep sea-land connection: interactive 3D visualization and molecular phylogeny of Bathyhedyle boucheti n. sp. (Bathyhedylidae n. fam.)-the first panpulmonate slug from bathyal zones.

    PubMed

    Neusser, Timea P; Jörger, Katharina M; Lodde-Bensch, Eva; Strong, Ellen E; Schrödl, Michael

    2016-01-01

    The deep sea comprises vast unexplored areas and is expected to conceal significant undescribed invertebrate species diversity. Deep waters may act as a refuge for many relictual groups, including elusive and enigmatic higher taxa, but the evolutionary pathways by which colonization of the deep sea has occurred have scarcely been investigated. Sister group relationships between shallow water and deep sea taxa have been documented in several invertebrate groups, but are unknown between amphibious/terrestrial and deep-sea species. Here we describe in full and interactive 3D morphoanatomical detail the new sea slug species Bathyhedyle boucheti n. sp., dredged from the continental slope off Mozambique. Molecular and morphological analyses reveal that it represents a novel heterobranch gastropod lineage which we establish as the new family Bathyhedylidae. The family is robustly supported as sister to the recently discovered panpulmonate acochlidian family Aitengidae, which comprises amphibious species living along the sea shore as well as fully terrestrial species. This is the first marine-epibenthic representative among hedylopsacean Acochlidiida, the first record of an acochlidian from deep waters and the first documented panpulmonate deep-sea slug. Considering a marine mesopsammic ancestor, the external morphological features of Bathyhedyle n. gen. may be interpreted as independent adaptations to a benthic life style in the deep sea, including the large body size, broad foot and propodial tentacles. Alternatively, the common ancestor of Bathyhedylidae and Aitengidae may have been a macroscopic amphibious or even terrestrial species. We hypothesize that oophagy in the common ancestor of Aitengidae and Bathyhedylidae might explain the impressive ecological and evolutionary flexibility in habitat choice in the Acochlidiida.

  15. Aircraft noise descriptor and its application

    NASA Astrophysics Data System (ADS)

    Igarashi, Juichi

    The methods and indices used in Japan to evaluate aircraft noise and the government-enforced countermeasures are discussed. The ECPNL descriptor was modified so as to make the new descriptor, WECPNL', approximately equivalent to Lden, and the noise contours were calculated for each airport in Japan. The government enforced the policy of land purchase within the WECPNL' of 85, and the houses within the value of 75 were declared as needing insulation. The noise descriptor Leq or Ldn has been used to describe human responses to various kinds of noises. However, a single value descriptor was found to have a limit of applicability, because the human response is not a linear function of a sound level. Another defect of the descriptor is a failure to represent the human response adequately for a small number of flights. It is noted that the house vibration caused by low-frequency components of aircraft noise cannot yet be evaluated.

  16. Sodium 3D COncentration MApping (COMA 3D) using 23Na and proton MRI

    NASA Astrophysics Data System (ADS)

    Truong, Milton L.; Harrington, Michael G.; Schepkin, Victor D.; Chekmenev, Eduard Y.

    2014-10-01

    Functional changes of sodium 3D MRI signals were converted into millimolar concentration changes using an open-source fully automated MATLAB toolbox. These concentration changes are visualized via 3D sodium concentration maps, and they are overlaid over conventional 3D proton images to provide high-resolution co-registration for easy correlation of functional changes to anatomical regions. Nearly 5000/h concentration maps were generated on a personal computer (ca. 2012) using 21.1 T 3D sodium MRI brain images of live rats with spatial resolution of 0.8 × 0.8 × 0.8 mm3 and imaging matrices of 60 × 60 × 60. The produced concentration maps allowed for non-invasive quantitative measurement of in vivo sodium concentration in the normal rat brain as a functional response to migraine-like conditions. The presented work can also be applied to sodium-associated changes in migraine, cancer, and other metabolic abnormalities that can be sensed by molecular imaging. The MATLAB toolbox allows for automated image analysis of the 3D images acquired on the Bruker platform and can be extended to other imaging platforms. The resulting images are presented in a form of series of 2D slices in all three dimensions in native MATLAB and PDF formats. The following is provided: (a) MATLAB source code for image processing, (b) the detailed processing procedures, (c) description of the code and all sub-routines, (d) example data sets of initial and processed data. The toolbox can be downloaded at: http://www.vuiis.vanderbilt.edu/~truongm/COMA3D/.

  17. Sodium 3D COncentration MApping (COMA 3D) Using 23Na and Proton MRI

    PubMed Central

    Truong, Milton L.; Harrington, Michael G.; Schepkin, Victor D.; Chekmenev, Eduard Y.

    2014-01-01

    Functional changes of sodium 3D MRI signals were converted into millimolar concentration changes using an open-source fully automated MATLAB toolbox. These concentration changes are visualized via 3D sodium concentration maps, and they are overlaid over conventional 3D proton images to provide high-resolution co-registration for easy correlation of functional changes to anatomical regions. Nearly 5000/hour concentration maps were generated on a personal computer (ca. 2012) using 21.1 T 3D sodium MRI brain images of live rats with spatial resolution of 0.8×0.8×0.8 mm3 and imaging matrices of 60×60×60. The produced concentration maps allowed for non-invasive quantitative measurement of in vivo sodium concentration in the normal rat brain as a functional response to migraine-like conditions. The presented work can also be applied to sodium-associated changes in migraine, cancer, and other metabolic abnormalities that can be sensed by molecular imaging. The MATLAB toolbox allows for automated image analysis of the 3D images acquired on the Bruker platform and can be extended to other imaging platforms. The resulting images are presented in a form of series of 2D slices in all three dimensions in native MATLAB and PDF formats. The following is provided: (a) MATLAB source code for image processing, (b) the detailed processing procedures, (c) description of the code and all sub-routines, (d) example data sets of initial and processed data. The toolbox can be downloaded at: http://www.vuiis.vanderbilt.edu/~truongm/COMA3D/ PMID:25261742

  18. Interactive 3D Mars Visualization

    NASA Technical Reports Server (NTRS)

    Powell, Mark W.

    2012-01-01

    The Interactive 3D Mars Visualization system provides high-performance, immersive visualization of satellite and surface vehicle imagery of Mars. The software can be used in mission operations to provide the most accurate position information for the Mars rovers to date. When integrated into the mission data pipeline, this system allows mission planners to view the location of the rover on Mars to 0.01-meter accuracy with respect to satellite imagery, with dynamic updates to incorporate the latest position information. Given this information so early in the planning process, rover drivers are able to plan more accurate drive activities for the rover than ever before, increasing the execution of science activities significantly. Scientifically, this 3D mapping information puts all of the science analyses to date into geologic context on a daily basis instead of weeks or months, as was the norm prior to this contribution. This allows the science planners to judge the efficacy of their previously executed science observations much more efficiently, and achieve greater science return as a result. The Interactive 3D Mars surface view is a Mars terrain browsing software interface that encompasses the entire region of exploration for a Mars surface exploration mission. The view is interactive, allowing the user to pan in any direction by clicking and dragging, or to zoom in or out by scrolling the mouse or touchpad. This set currently includes tools for selecting a point of interest, and a ruler tool for displaying the distance between and positions of two points of interest. The mapping information can be harvested and shared through ubiquitous online mapping tools like Google Mars, NASA WorldWind, and Worldwide Telescope.

  19. 3D Nanostructuring of Semiconductors

    NASA Astrophysics Data System (ADS)

    Blick, Robert

    2000-03-01

    Modern semiconductor technology allows to machine devices on the nanometer scale. I will discuss the current limits of the fabrication processes, which enable the definition of single electron transistors with dimensions down to 8 nm. In addition to the conventional 2D patterning and structuring of semiconductors, I will demonstrate how to apply 3D nanostructuring techniques to build freely suspended single-crystal beams with lateral dimension down to 20 nm. In transport measurements in the temperature range from 30 mK up to 100 K these nano-crystals are characterized regarding their electronic as well as their mechanical properties. Moreover, I will present possible applications of these devices.

  20. What Lies Ahead (3-D)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This 3-D cylindrical-perspective mosaic taken by the navigation camera on the Mars Exploration Rover Spirit on sol 82 shows the view south of the large crater dubbed 'Bonneville.' The rover will travel toward the Columbia Hills, seen here at the upper left. The rock dubbed 'Mazatzal' and the hole the rover drilled in to it can be seen at the lower left. The rover's position is referred to as 'Site 22, Position 32.' This image was geometrically corrected to make the horizon appear flat.

  1. Making Inexpensive 3-D Models

    NASA Astrophysics Data System (ADS)

    Manos, Harry

    2016-03-01

    Visual aids are important to student learning, and they help make the teacher's job easier. Keeping with the TPT theme of "The Art, Craft, and Science of Physics Teaching," the purpose of this article is to show how teachers, lacking equipment and funds, can construct a durable 3-D model reference frame and a model gravity well tailored to specific class lessons. Most of the supplies are readily available in the home or at school: rubbing alcohol, a rag, two colors of spray paint, art brushes, and masking tape. The cost of these supplies, if you don't have them, is less than 20.

  2. A Clean Adirondack (3-D)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This is a 3-D anaglyph showing a microscopic image taken of an area measuring 3 centimeters (1.2 inches) across on the rock called Adirondack. The image was taken at Gusev Crater on the 33rd day of the Mars Exploration Rover Spirit's journey (Feb. 5, 2004), after the rover used its rock abrasion tool brush to clean the surface of the rock. Dust, which was pushed off to the side during cleaning, can still be seen to the left and in low areas of the rock.

  3. 3D Printed Shelby Cobra

    SciTech Connect

    Love, Lonnie

    2015-01-09

    ORNL's newly printed 3D Shelby Cobra was showcased at the 2015 NAIAS in Detroit. This "laboratory on wheels" uses the Shelby Cobra design, celebrating the 50th anniversary of this model and honoring the first vehicle to be voted a national monument. The Shelby was printed at the Department of Energy’s Manufacturing Demonstration Facility at ORNL using the BAAM (Big Area Additive Manufacturing) machine and is intended as a “plug-n-play” laboratory on wheels. The Shelby will allow research and development of integrated components to be tested and enhanced in real time, improving the use of sustainable, digital manufacturing solutions in the automotive industry.

  4. 3D Ear Identification Based on Sparse Representation

    PubMed Central

    Zhang, Lin; Ding, Zhixuan; Li, Hongyu; Shen, Ying

    2014-01-01

    Biometrics based personal authentication is an effective way for automatically recognizing, with a high confidence, a person’s identity. Recently, 3D ear shape has attracted tremendous interests in research field due to its richness of feature and ease of acquisition. However, the existing ICP (Iterative Closet Point)-based 3D ear matching methods prevalent in the literature are not quite efficient to cope with the one-to-many identification case. In this paper, we aim to fill this gap by proposing a novel effective fully automatic 3D ear identification system. We at first propose an accurate and efficient template-based ear detection method. By utilizing such a method, the extracted ear regions are represented in a common canonical coordinate system determined by the ear contour template, which facilitates much the following stages of feature extraction and classification. For each extracted 3D ear, a feature vector is generated as its representation by making use of a PCA-based local feature descriptor. At the stage of classification, we resort to the sparse representation based classification approach, which actually solves an l1-minimization problem. To the best of our knowledge, this is the first work introducing the sparse representation framework into the field of 3D ear identification. Extensive experiments conducted on a benchmark dataset corroborate the effectiveness and efficiency of the proposed approach. The associated Matlab source code and the evaluation results have been made publicly online available at http://sse.tongji.edu.cn/linzhang/ear/srcear/srcear.htm. PMID:24740247

  5. Validation of image processing tools for 3-D fluorescence microscopy.

    PubMed

    Dieterlen, Alain; Xu, Chengqi; Gramain, Marie-Pierre; Haeberlé, Olivier; Colicchio, Bruno; Cudel, Christophe; Jacquey, Serge; Ginglinger, Emanuelle; Jung, Georges; Jeandidier, Eric

    2002-04-01

    3-D optical fluorescent microscopy becomes nowadays an efficient tool for volumic investigation of living biological samples. Using optical sectioning technique, a stack of 2-D images is obtained. However, due to the nature of the system optical transfer function and non-optimal experimental conditions, acquired raw data usually suffer from some distortions. In order to carry out biological analysis, raw data have to be restored by deconvolution. The system identification by the point-spread function is useful to obtain the knowledge of the actual system and experimental parameters, which is necessary to restore raw data. It is furthermore helpful to precise the experimental protocol. In order to facilitate the use of image processing techniques, a multi-platform-compatible software package called VIEW3D has been developed. It integrates a set of tools for the analysis of fluorescence images from 3-D wide-field or confocal microscopy. A number of regularisation parameters for data restoration are determined automatically. Common geometrical measurements and morphological descriptors of fluorescent sites are also implemented to facilitate the characterisation of biological samples. An example of this method concerning cytogenetics is presented.

  6. Positional Awareness Map 3D (PAM3D)

    NASA Technical Reports Server (NTRS)

    Hoffman, Monica; Allen, Earl L.; Yount, John W.; Norcross, April Louise

    2012-01-01

    The Western Aeronautical Test Range of the National Aeronautics and Space Administration s Dryden Flight Research Center needed to address the aging software and hardware of its current situational awareness display application, the Global Real-Time Interactive Map (GRIM). GRIM was initially developed in the late 1980s and executes on older PC architectures using a Linux operating system that is no longer supported. Additionally, the software is difficult to maintain due to its complexity and loss of developer knowledge. It was decided that a replacement application must be developed or acquired in the near future. The replacement must provide the functionality of the original system, the ability to monitor test flight vehicles in real-time, and add improvements such as high resolution imagery and true 3-dimensional capability. This paper will discuss the process of determining the best approach to replace GRIM, and the functionality and capabilities of the first release of the Positional Awareness Map 3D.

  7. 3D printed bionic ears.

    PubMed

    Mannoor, Manu S; Jiang, Ziwen; James, Teena; Kong, Yong Lin; Malatesta, Karen A; Soboyejo, Winston O; Verma, Naveen; Gracias, David H; McAlpine, Michael C

    2013-06-12

    The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing.

  8. 3D Printable Graphene Composite

    PubMed Central

    Wei, Xiaojun; Li, Dong; Jiang, Wei; Gu, Zheming; Wang, Xiaojuan; Zhang, Zengxing; Sun, Zhengzong

    2015-01-01

    In human being’s history, both the Iron Age and Silicon Age thrived after a matured massive processing technology was developed. Graphene is the most recent superior material which could potentially initialize another new material Age. However, while being exploited to its full extent, conventional processing methods fail to provide a link to today’s personalization tide. New technology should be ushered in. Three-dimensional (3D) printing fills the missing linkage between graphene materials and the digital mainstream. Their alliance could generate additional stream to push the graphene revolution into a new phase. Here we demonstrate for the first time, a graphene composite, with a graphene loading up to 5.6 wt%, can be 3D printable into computer-designed models. The composite’s linear thermal coefficient is below 75 ppm·°C−1 from room temperature to its glass transition temperature (Tg), which is crucial to build minute thermal stress during the printing process. PMID:26153673

  9. 3D Printed Bionic Ears

    PubMed Central

    Mannoor, Manu S.; Jiang, Ziwen; James, Teena; Kong, Yong Lin; Malatesta, Karen A.; Soboyejo, Winston O.; Verma, Naveen; Gracias, David H.; McAlpine, Michael C.

    2013-01-01

    The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. Conventional electronic devices are inherently two-dimensional, preventing seamless multidimensional integration with synthetic biology, as the processes and materials are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the precise anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing. PMID:23635097

  10. Martian terrain & airbags - 3D

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Portions of the lander's deflated airbags and a petal are at lower left in this image, taken in stereo by the Imager for Mars Pathfinder (IMP) on Sol 3. 3D glasses are necessary to identify surface detail. This image is part of a 3D 'monster' panorama of the area surrounding the landing site.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

    Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  11. Martian terrain & airbags - 3D

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Portions of the lander's deflated airbags and a petal are at the lower area of this image, taken in stereo by the Imager for Mars Pathfinder (IMP) on Sol 3. 3D glasses are necessary to identify surface detail. This image is part of a 3D 'monster' panorama of the area surrounding the landing site.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

    Click below to see the left and right views individually. [figure removed for brevity, see original site] Left [figure removed for brevity, see original site] Right

  12. 3D structured illumination microscopy

    NASA Astrophysics Data System (ADS)

    Dougherty, William M.; Goodwin, Paul C.

    2011-03-01

    Three-dimensional structured illumination microscopy achieves double the lateral and axial resolution of wide-field microscopy, using conventional fluorescent dyes, proteins and sample preparation techniques. A three-dimensional interference-fringe pattern excites the fluorescence, filling in the "missing cone" of the wide field optical transfer function, thereby enabling axial (z) discrimination. The pattern acts as a spatial carrier frequency that mixes with the higher spatial frequency components of the image, which usually succumb to the diffraction limit. The fluorescence image encodes the high frequency content as a down-mixed, moiré-like pattern. A series of images is required, wherein the 3D pattern is shifted and rotated, providing down-mixed data for a system of linear equations. Super-resolution is obtained by solving these equations. The speed with which the image series can be obtained can be a problem for the microscopy of living cells. Challenges include pattern-switching speeds, optical efficiency, wavefront quality and fringe contrast, fringe pitch optimization, and polarization issues. We will review some recent developments in 3D-SIM hardware with the goal of super-resolved z-stacks of motile cells.

  13. Analysis of 3D multi-layer microfluidic gradient generator.

    PubMed

    Ha, Jang Ho; Kim, Tae Hyeon; Lee, Jong Min; Ahrberg, Christian D; Chung, Bong Geun

    2017-01-01

    We developed a three-dimensional (3D) simple multi-layer microfluidic gradient generator to create molecular gradients on the centimeter scale with a wide range of flow rates. To create the concentration gradients, a main channel (MC) was orthogonally intersected with vertical side microchannel (SC) in a 3D multi-layer microfluidic device. Through sequential dilution from the SC, a spatial gradient was generated in the MC. Two theoretical models were created to assist in the design of the 3D multi-layer microfluidic gradient generator and to compare its performance against a two-dimensional equivalent. A first mass balance model was used to predict the steady-state concentrations reached, while a second computational fluid dynamic model was employed to predict spatial development of the gradient by considering convective as well as diffusive mass transport. Furthermore, the theoretical simulations were verified through experiments to create molecular gradients in a 3D multi-layer microfluidic gradient generator.

  14. Spherical blurred shape model for 3-D object and pose recognition: quantitative analysis and HCI applications in smart environments.

    PubMed

    Lopes, Oscar; Reyes, Miguel; Escalera, Sergio; Gonzàlez, Jordi

    2014-12-01

    The use of depth maps is of increasing interest after the advent of cheap multisensor devices based on structured light, such as Kinect. In this context, there is a strong need of powerful 3-D shape descriptors able to generate rich object representations. Although several 3-D descriptors have been already proposed in the literature, the research of discriminative and computationally efficient descriptors is still an open issue. In this paper, we propose a novel point cloud descriptor called spherical blurred shape model (SBSM) that successfully encodes the structure density and local variabilities of an object based on shape voxel distances and a neighborhood propagation strategy. The proposed SBSM is proven to be rotation and scale invariant, robust to noise and occlusions, highly discriminative for multiple categories of complex objects like the human hand, and computationally efficient since the SBSM complexity is linear to the number of object voxels. Experimental evaluation in public depth multiclass object data, 3-D facial expressions data, and a novel hand poses data sets show significant performance improvements in relation to state-of-the-art approaches. Moreover, the effectiveness of the proposal is also proved for object spotting in 3-D scenes and for real-time automatic hand pose recognition in human computer interaction scenarios.

  15. 3D Printing of Graphene Aerogels.

    PubMed

    Zhang, Qiangqiang; Zhang, Feng; Medarametla, Sai Pradeep; Li, Hui; Zhou, Chi; Lin, Dong

    2016-04-06

    3D printing of a graphene aerogel with true 3D overhang structures is highlighted. The aerogel is fabricated by combining drop-on-demand 3D printing and freeze casting. The water-based GO ink is ejected and freeze-cast into designed 3D structures. The lightweight (<10 mg cm(-3) ) 3D printed graphene aerogel presents superelastic and high electrical conduction.

  16. Quasi 3D dispersion experiment

    NASA Astrophysics Data System (ADS)

    Bakucz, P.

    2003-04-01

    This paper studies the problem of tracer dispersion in a coloured fluid flowing through a two-phase 3D rough channel-system in a 40 cm*40 cm plexi-container filled by homogen glass fractions and colourless fluid. The unstable interface between the driving coloured fluid and the colourless fluid develops viscous fingers with a fractal structure at high capillary number. Five two-dimensional fractal fronts have been observed at the same time using four cameras along the vertical side-walls and using one camera located above the plexi-container. In possession of five fronts the spatial concentration contours are determined using statistical models. The concentration contours are self-affine fractal curves with a fractal dimension D=2.19. This result is valid for disperison at high Péclet numbers.

  17. ShowMe3D

    SciTech Connect

    Sinclair, Michael B

    2012-01-05

    ShowMe3D is a data visualization graphical user interface specifically designed for use with hyperspectral image obtained from the Hyperspectral Confocal Microscope. The program allows the user to select and display any single image from a three dimensional hyperspectral image stack. By moving a slider control, the user can easily move between images of the stack. The user can zoom into any region of the image. The user can select any pixel or region from the displayed image and display the fluorescence spectrum associated with that pixel or region. The user can define up to 3 spectral filters to apply to the hyperspectral image and view the image as it would appear from a filter-based confocal microscope. The user can also obtain statistics such as intensity average and variance from selected regions.

  18. 3D Printed Shelby Cobra

    ScienceCinema

    Love, Lonnie

    2016-11-02

    ORNL's newly printed 3D Shelby Cobra was showcased at the 2015 NAIAS in Detroit. This "laboratory on wheels" uses the Shelby Cobra design, celebrating the 50th anniversary of this model and honoring the first vehicle to be voted a national monument. The Shelby was printed at the Department of Energy’s Manufacturing Demonstration Facility at ORNL using the BAAM (Big Area Additive Manufacturing) machine and is intended as a “plug-n-play” laboratory on wheels. The Shelby will allow research and development of integrated components to be tested and enhanced in real time, improving the use of sustainable, digital manufacturing solutions in the automotive industry.

  19. 3D QSAR studies on binding affinities of coumarin natural products for glycosomal GAPDH of Trypanosoma cruzi

    NASA Astrophysics Data System (ADS)

    Menezes, Irwin R. A.; Lopes, Julio C. D.; Montanari, Carlos A.; Oliva, Glaucius; Pavão, Fernando; Castilho, Marcelo S.; Vieira, Paulo C.; Pupo, M.^onica T.

    2003-05-01

    Drug design strategies based on Comparative Molecular Field Analysis (CoMFA) have been used to predict the activity of new compounds. The major advantage of this approach is that it permits the analysis of a large number of quantitative descriptors and uses chemometric methods such as partial least squares (PLS) to correlate changes in bioactivity with changes in chemical structure. Because it is often difficult to rationalize all variables affecting the binding affinity of compounds using CoMFA solely, the program GRID was used to describe ligands in terms of their molecular interaction fields, MIFs. The program VolSurf that is able to compress the relevant information present in 3D maps into a few descriptors can treat these GRID fields. The binding affinities of a new set of compounds consisting of 13 coumarins, for one of which the three-dimensional ligand-enzyme bound structure is known, were studied. A final model based on the mentioned programs was independently validated by synthesizing and testing new coumarin derivatives. By relying on our knowledge of the real physical data (i.e., combining crystallographic and binding affinity results), it is also shown that ligand-based design agrees with structure-based design. The compound with the highest binding affinity was the coumarin chalepin, isolated from Rutaceae species, with an IC50 value of 55.5 μM towards the enzyme glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from glycosomes of the parasite Trypanosoma cruzi, the causative agent of Chagas' disease. The proposed models from GRID MIFs have revealed the importance of lipophilic interactions in modulating the inhibition, but without excluding the dependence on stereo-electronic properties as found from CoMFA fields.

  20. Supernova Remnant in 3-D

    NASA Technical Reports Server (NTRS)

    2009-01-01

    wavelengths. Since the amount of the wavelength shift is related to the speed of motion, one can determine how fast the debris are moving in either direction. Because Cas A is the result of an explosion, the stellar debris is expanding radially outwards from the explosion center. Using simple geometry, the scientists were able to construct a 3-D model using all of this information. A program called 3-D Slicer modified for astronomical use by the Astronomical Medicine Project at Harvard University in Cambridge, Mass. was used to display and manipulate the 3-D model. Commercial software was then used to create the 3-D fly-through.

    The blue filaments defining the blast wave were not mapped using the Doppler effect because they emit a different kind of light synchrotron radiation that does not emit light at discrete wavelengths, but rather in a broad continuum. The blue filaments are only a representation of the actual filaments observed at the blast wave.

    This visualization shows that there are two main components to this supernova remnant: a spherical component in the outer parts of the remnant and a flattened (disk-like) component in the inner region. The spherical component consists of the outer layer of the star that exploded, probably made of helium and carbon. These layers drove a spherical blast wave into the diffuse gas surrounding the star. The flattened component that astronomers were unable to map into 3-D prior to these Spitzer observations consists of the inner layers of the star. It is made from various heavier elements, not all shown in the visualization, such as oxygen, neon, silicon, sulphur, argon and iron.

    High-velocity plumes, or jets, of this material are shooting out from the explosion in the plane of the disk-like component mentioned above. Plumes of silicon appear in the northeast and southwest, while those of iron are seen in the southeast and north. These jets were already known and Doppler velocity measurements have been made for these

  1. Exploring the role of quantum chemical descriptors in modeling acute toxicity of diverse chemicals to Daphnia magna.

    PubMed

    Reenu; Vikas

    2015-09-01

    Various quantum-mechanically computed molecular and thermodynamic descriptors along with physico-chemical, electrostatic and topological descriptors are compared while developing quantitative structure-activity relationships (QSARs) for the acute toxicity of 252 diverse organic chemicals towards Daphnia magna. QSAR models based on the quantum-chemical descriptors, computed with routinely employed advanced semi-empirical and ab-initio methods, along with the electron-correlation contribution (CORR) of the descriptors, are analyzed for the external predictivity of the acute toxicity. The models with reliable internal stability and external predictivity are found to be based on the HOMO energy along with the physico-chemical, electrostatic and topological descriptors. Besides this, the total energy and electron-correlation energy are also observed as highly reliable descriptors, suggesting that the intra-molecular interactions between the electrons play an important role in the origin of the acute toxicity, which is in fact an unexplored phenomenon. The models based on quantum-chemical descriptors such as chemical hardness, absolute electronegativity, standard Gibbs free energy and enthalpy are also observed to be reliable. A comparison of the robust models based on the quantum-chemical descriptors computed with various quantum-mechanical methods suggests that the advanced semi-empirical methods such as PM7 can be more reliable than the ab-initio methods which are computationally more expensive.

  2. Automatic feature detection for 3D surface reconstruction from HDTV endoscopic videos

    NASA Astrophysics Data System (ADS)

    Groch, Anja; Baumhauer, Matthias; Meinzer, Hans-Peter; Maier-Hein, Lena

    2010-02-01

    A growing number of applications in the field of computer-assisted laparoscopic interventions depend on accurate and fast 3D surface acquisition. The most commonly applied methods for 3D reconstruction of organ surfaces from 2D endoscopic images involve establishment of correspondences in image pairs to allow for computation of 3D point coordinates via triangulation. The popular feature-based approach for correspondence search applies a feature descriptor to compute high-dimensional feature vectors describing the characteristics of selected image points. Correspondences are established between image points with similar feature vectors. In a previous study, the performance of a large set of state-of-the art descriptors for the use in minimally invasive surgery was assessed. However, standard Phase Alternating Line (PAL) endoscopic images were utilized for this purpose. In this paper, we apply some of the best performing feature descriptors to in-vivo PAL endoscopic images as well as to High Definition Television (HDTV) endoscopic images of the same scene and show that the quality of the correspondences can be increased significantly when using high resolution images.

  3. 3D printing of microscopic bacterial communities

    PubMed Central

    Connell, Jodi L.; Ritschdorff, Eric T.; Whiteley, Marvin; Shear, Jason B.

    2013-01-01

    Bacteria communicate via short-range physical and chemical signals, interactions known to mediate quorum sensing, sporulation, and other adaptive phenotypes. Although most in vitro studies examine bacterial properties averaged over large populations, the levels of key molecular determinants of bacterial fitness and pathogenicity (e.g., oxygen, quorum-sensing signals) may vary over micrometer scales within small, dense cellular aggregates believed to play key roles in disease transmission. A detailed understanding of how cell–cell interactions contribute to pathogenicity in natural, complex environments will require a new level of control in constructing more relevant cellular models for assessing bacterial phenotypes. Here, we describe a microscopic three-dimensional (3D) printing strategy that enables multiple populations of bacteria to be organized within essentially any 3D geometry, including adjacent, nested, and free-floating colonies. In this laser-based lithographic technique, microscopic containers are formed around selected bacteria suspended in gelatin via focal cross-linking of polypeptide molecules. After excess reagent is removed, trapped bacteria are localized within sealed cavities formed by the cross-linked gelatin, a highly porous material that supports rapid growth of fully enclosed cellular populations and readily transmits numerous biologically active species, including polypeptides, antibiotics, and quorum-sensing signals. Using this approach, we show that a picoliter-volume aggregate of Staphylococcus aureus can display substantial resistance to β-lactam antibiotics by enclosure within a shell composed of Pseudomonas aeruginosa. PMID:24101503

  4. Petals' shape descriptor for blooming flowers recognition

    NASA Astrophysics Data System (ADS)

    Tan, Wooi-Nee; Tan, Yi-Fei; Koo, Ah-Choo; Lim, Yan-Peng

    2012-04-01

    This paper proposes a new descriptor to identify the petals' shape of a blooming flower based on the digital images captured in natural scene. The proposed descriptor can be used as one of features in computer aided flower recognition system beside the commonly used features such as number of petals and color. Experiments were conducted on the Malaysia flowers with same number of petals and with similar color across different species of flowers. 35 images from 7 species were used as the training set to set up the reference values of petals' shape descriptor and 7 new images were used as the testing set. The descriptor calculated from the testing set is then compared to the reference values from the training set to achieve the flowers recognition purpose. With the given set of data, complete success in full identification rate was obtained.

  5. 3D Kitaev spin liquids

    NASA Astrophysics Data System (ADS)

    Hermanns, Maria

    The Kitaev honeycomb model has become one of the archetypal spin models exhibiting topological phases of matter, where the magnetic moments fractionalize into Majorana fermions interacting with a Z2 gauge field. In this talk, we discuss generalizations of this model to three-dimensional lattice structures. Our main focus is the metallic state that the emergent Majorana fermions form. In particular, we discuss the relation of the nature of this Majorana metal to the details of the underlying lattice structure. Besides (almost) conventional metals with a Majorana Fermi surface, one also finds various realizations of Dirac semi-metals, where the gapless modes form Fermi lines or even Weyl nodes. We introduce a general classification of these gapless quantum spin liquids using projective symmetry analysis. Furthermore, we briefly outline why these Majorana metals in 3D Kitaev systems provide an even richer variety of Dirac and Weyl phases than possible for electronic matter and comment on possible experimental signatures. Work done in collaboration with Kevin O'Brien and Simon Trebst.

  6. 3D multiplexed immunoplasmonics microscopy

    NASA Astrophysics Data System (ADS)

    Bergeron, Éric; Patskovsky, Sergiy; Rioux, David; Meunier, Michel

    2016-07-01

    Selective labelling, identification and spatial distribution of cell surface biomarkers can provide important clinical information, such as distinction between healthy and diseased cells, evolution of a disease and selection of the optimal patient-specific treatment. Immunofluorescence is the gold standard for efficient detection of biomarkers expressed by cells. However, antibodies (Abs) conjugated to fluorescent dyes remain limited by their photobleaching, high sensitivity to the environment, low light intensity, and wide absorption and emission spectra. Immunoplasmonics is a novel microscopy method based on the visualization of Abs-functionalized plasmonic nanoparticles (fNPs) targeting cell surface biomarkers. Tunable fNPs should provide higher multiplexing capacity than immunofluorescence since NPs are photostable over time, strongly scatter light at their plasmon peak wavelengths and can be easily functionalized. In this article, we experimentally demonstrate accurate multiplexed detection based on the immunoplasmonics approach. First, we achieve the selective labelling of three targeted cell surface biomarkers (cluster of differentiation 44 (CD44), epidermal growth factor receptor (EGFR) and voltage-gated K+ channel subunit KV1.1) on human cancer CD44+ EGFR+ KV1.1+ MDA-MB-231 cells and reference CD44- EGFR- KV1.1+ 661W cells. The labelling efficiency with three stable specific immunoplasmonics labels (functionalized silver nanospheres (CD44-AgNSs), gold (Au) NSs (EGFR-AuNSs) and Au nanorods (KV1.1-AuNRs)) detected by reflected light microscopy (RLM) is similar to the one with immunofluorescence. Second, we introduce an improved method for 3D localization and spectral identification of fNPs based on fast z-scanning by RLM with three spectral filters corresponding to the plasmon peak wavelengths of the immunoplasmonics labels in the cellular environment (500 nm for 80 nm AgNSs, 580 nm for 100 nm AuNSs and 700 nm for 40 nm × 92 nm AuNRs). Third, the developed

  7. Crowdsourcing Based 3d Modeling

    NASA Astrophysics Data System (ADS)

    Somogyi, A.; Barsi, A.; Molnar, B.; Lovas, T.

    2016-06-01

    Web-based photo albums that support organizing and viewing the users' images are widely used. These services provide a convenient solution for storing, editing and sharing images. In many cases, the users attach geotags to the images in order to enable using them e.g. in location based applications on social networks. Our paper discusses a procedure that collects open access images from a site frequently visited by tourists. Geotagged pictures showing the image of a sight or tourist attraction are selected and processed in photogrammetric processing software that produces the 3D model of the captured object. For the particular investigation we selected three attractions in Budapest. To assess the geometrical accuracy, we used laser scanner and DSLR as well as smart phone photography to derive reference values to enable verifying the spatial model obtained from the web-album images. The investigation shows how detailed and accurate models could be derived applying photogrammetric processing software, simply by using images of the community, without visiting the site.

  8. Midsagittal plane extraction from brain images based on 3D SIFT

    NASA Astrophysics Data System (ADS)

    Wu, Huisi; Wang, Defeng; Shi, Lin; Wen, Zhenkun; Ming, Zhong

    2014-03-01

    Midsagittal plane (MSP) extraction from 3D brain images is considered as a promising technique for human brain symmetry analysis. In this paper, we present a fast and robust MSP extraction method based on 3D scale-invariant feature transform (SIFT). Unlike the existing brain MSP extraction methods, which mainly rely on the gray similarity, 3D edge registration or parameterized surface matching to determine the fissure plane, our proposed method is based on distinctive 3D SIFT features, in which the fissure plane is determined by parallel 3D SIFT matching and iterative least-median of squares plane regression. By considering the relative scales, orientations and flipped descriptors between two 3D SIFT features, we propose a novel metric to measure the symmetry magnitude for 3D SIFT features. By clustering and indexing the extracted SIFT features using a k-dimensional tree (KD-tree) implemented on graphics processing units, we can match multiple pairs of 3D SIFT features in parallel and solve the optimal MSP on-the-fly. The proposed method is evaluated by synthetic and in vivo datasets, of normal and pathological cases, and validated by comparisons with the state-of-the-art methods. Experimental results demonstrated that our method has achieved a real-time performance with better accuracy yielding an average yaw angle error below 0.91° and an average roll angle error no more than 0.89°.

  9. Progressive Shape-Distribution-Encoder for Learning 3D Shape Representation.

    PubMed

    Xie, Jin; Zhu, Fan; Dai, Guoxian; Shao, Ling; Fang, Yi

    2017-03-01

    Since there are complex geometric variations with 3D shapes, extracting efficient 3D shape features is one of the most challenging tasks in shape matching and retrieval. In this paper, we propose a deep shape descriptor by learning shape distributions at different diffusion time via a progressive shape-distribution-encoder (PSDE). First, we develop a shape distribution representation with the kernel density estimator to characterize the intrinsic geometry structures of 3D shapes. Then, we propose to learn a deep shape feature through an unsupervised PSDE. Specially, the unsupervised PSDE aims at modeling the complex non-linear transform of the estimated shape distributions between consecutive diffusion time. In order to characterize the intrinsic structures of 3D shapes more efficiently, we stack multiple PSDEs to form a network structure. Finally, we concatenate all neurons in the middle hidden layers of the unsupervised PSDE network to form an unsupervised shape descriptor for retrieval. Furthermore, by imposing an additional constraint on the outputs of all hidden layers, we propose a supervised PSDE to form a supervised shape descriptor. For each hidden layer, the similarity between a pair of outputs from the same class is as large as possible and the similarity between a pair of outputs from different classes is as small as possible. The proposed method is evaluated on three benchmark 3D shape data sets with large geometric variations, i.e., McGill, SHREC'10 ShapeGoogle, and SHREC'14 Human data sets, and the experimental results demonstrate the superiority of the proposed method to the existing approaches.

  10. PROFEAT Update: A Protein Features Web Server with Added Facility to Compute Network Descriptors for Studying Omics-Derived Networks.

    PubMed

    Zhang, P; Tao, L; Zeng, X; Qin, C; Chen, S Y; Zhu, F; Yang, S Y; Li, Z R; Chen, W P; Chen, Y Z

    2017-02-03

    The studies of biological, disease, and pharmacological networks are facilitated by the systems-level investigations using computational tools. In particular, the network descriptors developed in other disciplines have found increasing applications in the study of the protein, gene regulatory, metabolic, disease, and drug-targeted networks. Facilities are provided by the public web servers for computing network descriptors, but many descriptors are not covered, including those used or useful for biological studies. We upgraded the PROFEAT web server http://bidd2.nus.edu.sg/cgi-bin/profeat2016/main.cgi for computing up to 329 network descriptors and protein-protein interaction descriptors. PROFEAT network descriptors comprehensively describe the topological and connectivity characteristics of unweighted (uniform binding constants and molecular levels), edge-weighted (varying binding constants), node-weighted (varying molecular levels), edge-node-weighted (varying binding constants and molecular levels), and directed (oriented processes) networks. The usefulness of the network descriptors is illustrated by the literature-reported studies of the biological networks derived from the genome, interactome, transcriptome, metabolome, and diseasome profiles.

  11. Reduction of Thermal Conductivity by Nanoscale 3D Phononic Crystal

    PubMed Central

    Yang, Lina; Yang, Nuo; Li, Baowen

    2013-01-01

    We studied how the period length and the mass ratio affect the thermal conductivity of isotopic nanoscale three-dimensional (3D) phononic crystal of Si. Simulation results by equilibrium molecular dynamics show isotopic nanoscale 3D phononic crystals can significantly reduce the thermal conductivity of bulk Si at high temperature (1000 K), which leads to a larger ZT than unity. The thermal conductivity decreases as the period length and mass ratio increases. The phonon dispersion curves show an obvious decrease of group velocities in 3D phononic crystals. The phonon's localization and band gap is also clearly observed in spectra of normalized inverse participation ratio in nanoscale 3D phononic crystal. PMID:23378898

  12. Microscopy in 3D: a biologist’s toolbox

    PubMed Central

    Fischer, Robert S.; Wu, Yicong; Kanchanawong, Pakorn; Shroff, Hari; Waterman, Clare M.

    2012-01-01

    The power of fluorescence microscopy to study cellular structures and macromolecular complexes spans a wide range of size scales, from studies of cell behavior and function in physiological, three-dimensional (3D) environments, to understanding the molecular architecture of organelles. At each length scale, the challenge in 3D imaging is to extract the most spatial and temporal resolution possible while limiting photodamage/bleaching to living cells. A number of advancements in 3D fluorescence microscopy now offer higher resolution, improved speed, and reduced photobleaching relative to traditional point-scanning microscopy methods. Here, we discuss a few specific microscopy modalities that we believe will be particularly advantageous in imaging cells and subcellular structures in physiologically relevant 3D environments. PMID:22047760

  13. Reduction of thermal conductivity by nanoscale 3D phononic crystal.

    PubMed

    Yang, Lina; Yang, Nuo; Li, Baowen

    2013-01-01

    We studied how the period length and the mass ratio affect the thermal conductivity of isotopic nanoscale three-dimensional (3D) phononic crystal of Si. Simulation results by equilibrium molecular dynamics show isotopic nanoscale 3D phononic crystals can significantly reduce the thermal conductivity of bulk Si at high temperature (1000 K), which leads to a larger ZT than unity. The thermal conductivity decreases as the period length and mass ratio increases. The phonon dispersion curves show an obvious decrease of group velocities in 3D phononic crystals. The phonon's localization and band gap is also clearly observed in spectra of normalized inverse participation ratio in nanoscale 3D phononic crystal.

  14. Shape Signatures: New Descriptors for Predicting Cardiotoxicity In Silico

    PubMed Central

    Chekmarev, Dmitriy S.; Kholodovych, Vladyslav; Balakin, Konstantin V.; Ivanenkov, Yan; Ekins, Sean; Welsh, William J.

    2009-01-01

    Shape Signatures is a new computational tool that is being evaluated for applications in computational toxicology and drug discovery. The method employs a customized ray-tracing algorithm to explore the volume enclosed by the surface of a molecule and then uses the output to construct compact histograms (i.e., signatures) that encode for molecular shape and polarity. In the present study, we extend the application of the Shape Signatures methodology to the domain of computational models for cardiotoxicity. The Shape Signatures method is used to generate molecular descriptors that are then utilized with widely used classification techniques such as k nearest neighbors (k-NN), support vector machines (SVM), and Kohonen self-organizing maps (SOM). The performances of these approaches were assessed by applying them to a data set of compounds with varying affinity toward the 5-HT2B receptor as well as a set of human ether-a-go-go-related gene (hERG) potassium channel inhibitors. Our classification models for 5-HT2B represented the first attempt at global computational models for this receptor and exhibited average accuracies in the range of 73−83%. This level of performance is comparable to using commercially available molecular descriptors. The overall accuracy of the hERG Shape Signatures–SVM models was 69−73%, in line with other computational models published to date. Our data indicate that Shape Signatures descriptors can be used with SVM and Kohonen SOM and perform better in classification problems related to the analysis of highly clustered and heterogeneous property spaces. Such models may have utility for predicting the potential for cardiotoxicity in drug discovery mediated by the 5-HT2B receptor and hERG. PMID:18461975

  15. [3D emulation of epicardium dynamic mapping].

    PubMed

    Lu, Jun; Yang, Cui-Wei; Fang, Zu-Xiang

    2005-03-01

    In order to realize epicardium dynamic mapping of the whole atria, 3-D graphics are drawn with OpenGL. Some source codes are introduced in the paper to explain how to produce, read, and manipulate 3-D model data.

  16. An interactive multiview 3D display system

    NASA Astrophysics Data System (ADS)

    Zhang, Zhaoxing; Geng, Zheng; Zhang, Mei; Dong, Hui

    2013-03-01

    The progresses in 3D display systems and user interaction technologies will help more effective 3D visualization of 3D information. They yield a realistic representation of 3D objects and simplifies our understanding to the complexity of 3D objects and spatial relationship among them. In this paper, we describe an autostereoscopic multiview 3D display system with capability of real-time user interaction. Design principle of this autostereoscopic multiview 3D display system is presented, together with the details of its hardware/software architecture. A prototype is built and tested based upon multi-projectors and horizontal optical anisotropic display structure. Experimental results illustrate the effectiveness of this novel 3D display and user interaction system.

  17. Comparison of Different 2D and 3D-QSAR Methods on Activity Prediction of Histamine H3 Receptor Antagonists.

    PubMed

    Dastmalchi, Siavoush; Hamzeh-Mivehroud, Maryam; Asadpour-Zeynali, Karim

    2012-01-01

    Histamine H3 receptor subtype has been the target of several recent drug development programs. Quantitative structure-activity relationship (QSAR) methods are used to predict the pharmaceutically relevant properties of drug candidates whenever it is applicable. The aim of this study was to compare the predictive powers of three different QSAR techniques, namely, multiple linear regression (MLR), artificial neural network (ANN), and HASL as a 3D QSAR method, in predicting the receptor binding affinities of arylbenzofuran histamine H3 receptor antagonists. Genetic algorithm coupled partial least square as well as stepwise multiple regression methods were used to select a number of calculated molecular descriptors to be used in MLR and ANN-based QSAR studies. Using the leave-group-out cross-validation technique, the performances of the MLR and ANN methods were evaluated. The calculated values for the mean absolute percentage error (MAPE), ranging from 2.9 to 3.6, and standard deviation of error of prediction (SDEP), ranging from 0.31 to 0.36, for both MLR and ANN methods were statistically comparable, indicating that both methods perform equally well in predicting the binding affinities of the studied compounds toward the H3 receptors. On the other hand, the results from 3D-QSAR studies using HASL method were not as good as those obtained by 2D methods. It can be concluded that simple traditional approaches such as MLR method can be as reliable as those of more advanced and sophisticated methods like ANN and 3D-QSAR analyses.

  18. Laser Based 3D Volumetric Display System

    DTIC Science & Technology

    1993-03-01

    Literature, Costa Mesa, CA July 1983. 3. "A Real Time Autostereoscopic Multiplanar 3D Display System", Rodney Don Williams, Felix Garcia, Jr., Texas...8217 .- NUMBERS LASER BASED 3D VOLUMETRIC DISPLAY SYSTEM PR: CD13 0. AUTHOR(S) PE: N/AWIU: DN303151 P. Soltan, J. Trias, W. Robinson, W. Dahlke 7...laser generated 3D volumetric images on a rotating double helix, (where the 3D displays are computer controlled for group viewing with the naked eye

  19. True 3d Images and Their Applications

    NASA Astrophysics Data System (ADS)

    Wang, Z.; wang@hzgeospace., zheng.

    2012-07-01

    A true 3D image is a geo-referenced image. Besides having its radiometric information, it also has true 3Dground coordinates XYZ for every pixels of it. For a true 3D image, especially a true 3D oblique image, it has true 3D coordinates not only for building roofs and/or open grounds, but also for all other visible objects on the ground, such as visible building walls/windows and even trees. The true 3D image breaks the 2D barrier of the traditional orthophotos by introducing the third dimension (elevation) into the image. From a true 3D image, for example, people will not only be able to read a building's location (XY), but also its height (Z). true 3D images will fundamentally change, if not revolutionize, the way people display, look, extract, use, and represent the geospatial information from imagery. In many areas, true 3D images can make profound impacts on the ways of how geospatial information is represented, how true 3D ground modeling is performed, and how the real world scenes are presented. This paper first gives a definition and description of a true 3D image and followed by a brief review of what key advancements of geospatial technologies have made the creation of true 3D images possible. Next, the paper introduces what a true 3D image is made of. Then, the paper discusses some possible contributions and impacts the true 3D images can make to geospatial information fields. At the end, the paper presents a list of the benefits of having and using true 3D images and the applications of true 3D images in a couple of 3D city modeling projects.

  20. 3D Printing and Its Urologic Applications

    PubMed Central

    Soliman, Youssef; Feibus, Allison H; Baum, Neil

    2015-01-01

    3D printing is the development of 3D objects via an additive process in which successive layers of material are applied under computer control. This article discusses 3D printing, with an emphasis on its historical context and its potential use in the field of urology. PMID:26028997

  1. Teaching Geography with 3-D Visualization Technology

    ERIC Educational Resources Information Center

    Anthamatten, Peter; Ziegler, Susy S.

    2006-01-01

    Technology that helps students view images in three dimensions (3-D) can support a broad range of learning styles. "Geo-Wall systems" are visualization tools that allow scientists, teachers, and students to project stereographic images and view them in 3-D. We developed and presented 3-D visualization exercises in several undergraduate courses.…

  2. Expanding Geometry Understanding with 3D Printing

    ERIC Educational Resources Information Center

    Cochran, Jill A.; Cochran, Zane; Laney, Kendra; Dean, Mandi

    2016-01-01

    With the rise of personal desktop 3D printing, a wide spectrum of educational opportunities has become available for educators to leverage this technology in their classrooms. Until recently, the ability to create physical 3D models was well beyond the scope, skill, and budget of many schools. However, since desktop 3D printers have become readily…

  3. Beowulf 3D: a case study

    NASA Astrophysics Data System (ADS)

    Engle, Rob

    2008-02-01

    This paper discusses the creative and technical challenges encountered during the production of "Beowulf 3D," director Robert Zemeckis' adaptation of the Old English epic poem and the first film to be simultaneously released in IMAX 3D and digital 3D formats.

  4. 3D Flow Visualization Using Texture Advection

    NASA Technical Reports Server (NTRS)

    Kao, David; Zhang, Bing; Kim, Kwansik; Pang, Alex; Moran, Pat (Technical Monitor)

    2001-01-01

    Texture advection is an effective tool for animating and investigating 2D flows. In this paper, we discuss how this technique can be extended to 3D flows. In particular, we examine the use of 3D and 4D textures on 3D synthetic and computational fluid dynamics flow fields.

  5. Characterization of cerebral aneurysms using 3D moment invariants

    NASA Astrophysics Data System (ADS)

    Millan, Raul D.; Hernandez, Monica; Gallardo, Daniel; Cebral, Juan R.; Putman, Christopher; Dempere-Marco, Laura; Frangi, Alejandro F.

    2005-04-01

    The rupture mechanism of intracranial aneurysms is still not fully understood. Although the size of the aneurysm is the shape index most commonly used to predict rupture, some controversy still exists about its adequateness as an aneurysm rupture predictor. In this work, an automatic method to geometrically characterize the shape of cerebral saccular aneurysms using 3D moment invariants is proposed. Geometric moments are efficiently computed via application of the Divergence Theorem over the aneurysm surface using a non-structured mesh. 3D models of the aneurysm and its connected parent vessels have been reconstructed from segmentations of both 3DRA and CTA images. Two alternative approaches have been used for segmentation, the first one based on isosurface deformable models, and the second one based on the level set method. Several experiments were also conducted to both assess the influence of pre-processing steps in the stability of the aneurysm shape descriptors, and to know the robustness of the proposed method. Moment invariants have proved to be a robust technique while providing a reliable way to discriminate between ruptured and unruptured aneurysms (Sensitivity=0.83, Specificity=0.74) on a data set containing 55 aneurysms. Further investigation over larger databases is necessary to establish their adequateness as reliable predictors of rupture risk.

  6. 3-D Perspective Pasadena, California

    NASA Technical Reports Server (NTRS)

    2000-01-01

    This perspective view shows the western part of the city of Pasadena, California, looking north towards the San Gabriel Mountains. Portions of the cities of Altadena and La Canada, Flintridge are also shown. The image was created from three datasets: the Shuttle Radar Topography Mission (SRTM) supplied the elevation data; Landsat data from November 11, 1986 provided the land surface color (not the sky) and U.S. Geological Survey digital aerial photography provides the image detail. The Rose Bowl, surrounded by a golf course, is the circular feature at the bottom center of the image. The Jet Propulsion Laboratory is the cluster of large buildings north of the Rose Bowl at the base of the mountains. A large landfill, Scholl Canyon, is the smooth area in the lower left corner of the scene. This image shows the power of combining data from different sources to create planning tools to study problems that affect large urban areas. In addition to the well-known earthquake hazards, Southern California is affected by a natural cycle of fire and mudflows. Wildfires strip the mountains of vegetation, increasing the hazards from flooding and mudflows for several years afterwards. Data such as shown on this image can be used to predict both how wildfires will spread over the terrain and also how mudflows will be channeled down the canyons. The Shuttle Radar Topography Mission (SRTM), launched on February 11, 2000, uses the same radar instrument that comprised the Spaceborne Imaging Radar-C/X-Band Synthetic Aperture Radar (SIR-C/X-SAR) that flew twice on the Space Shuttle Endeavour in 1994. The mission was designed to collect three dimensional measurements of the Earth's surface. To collect the 3-D data, engineers added a 60-meter-long (200-foot) mast, an additional C-band imaging antenna and improved tracking and navigation devices. The mission is a cooperative project between the National Aeronautics and Space Administration (NASA), the National Imagery and Mapping Agency

  7. Rapid object indexing using locality sensitive hashing and joint 3D-signature space estimation.

    PubMed

    Matei, Bogdan; Shan, Ying; Sawhney, Harpreet S; Tan, Yi; Kumar, Rakesh; Huber, Daniel; Hebert, Martial

    2006-07-01

    We propose a new method for rapid 3D object indexing that combines feature-based methods with coarse alignment-based matching techniques. Our approach achieves a sublinear complexity on the number of models, maintaining at the same time a high degree of performance for real 3D sensed data that is acquired in largely uncontrolled settings. The key component of our method is to first index surface descriptors computed at salient locations from the scene into the whole model database using the Locality Sensitive Hashing (LSH), a probabilistic approximate nearest neighbor method. Progressively complex geometric constraints are subsequently enforced to further prune the initial candidates and eliminate false correspondences due to inaccuracies in the surface descriptors and the errors of the LSH algorithm. The indexed models are selected based on the MAP rule using posterior probability of the models estimated in the joint 3D-signature space. Experiments with real 3D data employing a large database of vehicles, most of them very similar in shape, containing 1,000,000 features from more than 365 models demonstrate a high degree of performance in the presence of occlusion and obscuration, unmodeled vehicle interiors and part articulations, with an average processing time between 50 and 100 seconds per query.

  8. Case study: Beauty and the Beast 3D: benefits of 3D viewing for 2D to 3D conversion

    NASA Astrophysics Data System (ADS)

    Handy Turner, Tara

    2010-02-01

    From the earliest stages of the Beauty and the Beast 3D conversion project, the advantages of accurate desk-side 3D viewing was evident. While designing and testing the 2D to 3D conversion process, the engineering team at Walt Disney Animation Studios proposed a 3D viewing configuration that not only allowed artists to "compose" stereoscopic 3D but also improved efficiency by allowing artists to instantly detect which image features were essential to the stereoscopic appeal of a shot and which features had minimal or even negative impact. At a time when few commercial 3D monitors were available and few software packages provided 3D desk-side output, the team designed their own prototype devices and collaborated with vendors to create a "3D composing" workstation. This paper outlines the display technologies explored, final choices made for Beauty and the Beast 3D, wish-lists for future development and a few rules of thumb for composing compelling 2D to 3D conversions.

  9. Mini 3D for shallow gas reconnaissance

    SciTech Connect

    Vallieres, T. des; Enns, D.; Kuehn, H.; Parron, D.; Lafet, Y.; Van Hulle, D.

    1996-12-31

    The Mini 3D project was undertaken by TOTAL and ELF with the support of CEPM (Comite d`Etudes Petrolieres et Marines) to define an economical method of obtaining 3D seismic HR data for shallow gas assessment. An experimental 3D survey was carried out with classical site survey techniques in the North Sea. From these data 19 simulations, were produced to compare different acquisition geometries ranging from dual, 600 m long cables to a single receiver. Results show that short offset, low fold and very simple streamer positioning are sufficient to give a reliable 3D image of gas charged bodies. The 3D data allow a much more accurate risk delineation than 2D HR data. Moreover on financial grounds Mini-3D is comparable in cost to a classical HR 2D survey. In view of these results, such HR 3D should now be the standard for shallow gas surveying.

  10. Replenishing data descriptors in a DMA injection FIFO buffer

    DOEpatents

    Archer, Charles J [Rochester, MN; Blocksome, Michael A [Rochester, MN; Cernohous, Bob R [Rochester, MN; Heidelberger, Philip [Cortlandt Manor, NY; Kumar, Sameer [White Plains, NY; Parker, Jeffrey J [Rochester, MN

    2011-10-11

    Methods, apparatus, and products are disclosed for replenishing data descriptors in a Direct Memory Access (`DMA`) injection first-in-first-out (`FIFO`) buffer that include: determining, by a messaging module on an origin compute node, whether a number of data descriptors in a DMA injection FIFO buffer exceeds a predetermined threshold, each data descriptor specifying an application message for transmission to a target compute node; queuing, by the messaging module, a plurality of new data descriptors in a pending descriptor queue if the number of the data descriptors in the DMA injection FIFO buffer exceeds the predetermined threshold; establishing, by the messaging module, interrupt criteria that specify when to replenish the injection FIFO buffer with the plurality of new data descriptors in the pending descriptor queue; and injecting, by the messaging module, the plurality of new data descriptors into the injection FIFO buffer in dependence upon the interrupt criteria.

  11. 3D Printing of Biomolecular Models for Research and Pedagogy.

    PubMed

    Da Veiga Beltrame, Eduardo; Tyrwhitt-Drake, James; Roy, Ian; Shalaby, Raed; Suckale, Jakob; Pomeranz Krummel, Daniel

    2017-03-13

    The construction of physical three-dimensional (3D) models of biomolecules can uniquely contribute to the study of the structure-function relationship. 3D structures are most often perceived using the two-dimensional and exclusively visual medium of the computer screen. Converting digital 3D molecular data into real objects enables information to be perceived through an expanded range of human senses, including direct stereoscopic vision, touch, and interaction. Such tangible models facilitate new insights, enable hypothesis testing, and serve as psychological or sensory anchors for conceptual information about the functions of biomolecules. Recent advances in consumer 3D printing technology enable, for the first time, the cost-effective fabrication of high-quality and scientifically accurate models of biomolecules in a variety of molecular representations. However, the optimization of the virtual model and its printing parameters is difficult and time consuming without detailed guidance. Here, we provide a guide on the digital design and physical fabrication of biomolecule models for research and pedagogy using open source or low-cost software and low-cost 3D printers that use fused filament fabrication technology.

  12. Mammographic images segmentation using texture descriptors.

    PubMed

    Mascaro, Angelica A; Mello, Carlos A B; Santos, Wellington P; Cavalcanti, George D C

    2009-01-01

    Tissue classification in mammography can help the diagnosis of breast cancer by separating healthy tissue from lesions. We present herein the use of three texture descriptors for breast tissue segmentation purposes: the Sum Histogram, the Gray Level Co-Occurrence Matrix (GLCM) and the Local Binary Pattern (LBP). A modification of the LBP is also proposed for a better distinction of the tissues. In order to segment the image into its tissues, these descriptors are compared using a fidelity index and two clustering algorithms: k-Means and SOM (Self-Organizing Maps).

  13. 3-D Technology Approaches for Biological Ecologies

    NASA Astrophysics Data System (ADS)

    Liu, Liyu; Austin, Robert; U. S-China Physical-Oncology Sciences Alliance (PS-OA) Team

    Constructing three dimensional (3-D) landscapes is an inevitable issue in deep study of biological ecologies, because in whatever scales in nature, all of the ecosystems are composed by complex 3-D environments and biological behaviors. Just imagine if a 3-D technology could help complex ecosystems be built easily and mimic in vivo microenvironment realistically with flexible environmental controls, it will be a fantastic and powerful thrust to assist researchers for explorations. For years, we have been utilizing and developing different technologies for constructing 3-D micro landscapes for biophysics studies in in vitro. Here, I will review our past efforts, including probing cancer cell invasiveness with 3-D silicon based Tepuis, constructing 3-D microenvironment for cell invasion and metastasis through polydimethylsiloxane (PDMS) soft lithography, as well as explorations of optimized stenting positions for coronary bifurcation disease with 3-D wax printing and the latest home designed 3-D bio-printer. Although 3-D technologies is currently considered not mature enough for arbitrary 3-D micro-ecological models with easy design and fabrication, I hope through my talk, the audiences will be able to sense its significance and predictable breakthroughs in the near future. This work was supported by the State Key Development Program for Basic Research of China (Grant No. 2013CB837200), the National Natural Science Foundation of China (Grant No. 11474345) and the Beijing Natural Science Foundation (Grant No. 7154221).

  14. 3D change detection - Approaches and applications

    NASA Astrophysics Data System (ADS)

    Qin, Rongjun; Tian, Jiaojiao; Reinartz, Peter

    2016-12-01

    Due to the unprecedented technology development of sensors, platforms and algorithms for 3D data acquisition and generation, 3D spaceborne, airborne and close-range data, in the form of image based, Light Detection and Ranging (LiDAR) based point clouds, Digital Elevation Models (DEM) and 3D city models, become more accessible than ever before. Change detection (CD) or time-series data analysis in 3D has gained great attention due to its capability of providing volumetric dynamics to facilitate more applications and provide more accurate results. The state-of-the-art CD reviews aim to provide a comprehensive synthesis and to simplify the taxonomy of the traditional remote sensing CD techniques, which mainly sit within the boundary of 2D image/spectrum analysis, largely ignoring the particularities of 3D aspects of the data. The inclusion of 3D data for change detection (termed 3D CD), not only provides a source with different modality for analysis, but also transcends the border of traditional top-view 2D pixel/object-based analysis to highly detailed, oblique view or voxel-based geometric analysis. This paper reviews the recent developments and applications of 3D CD using remote sensing and close-range data, in support of both academia and industry researchers who seek for solutions in detecting and analyzing 3D dynamics of various objects of interest. We first describe the general considerations of 3D CD problems in different processing stages and identify CD types based on the information used, being the geometric comparison and geometric-spectral analysis. We then summarize relevant works and practices in urban, environment, ecology and civil applications, etc. Given the broad spectrum of applications and different types of 3D data, we discuss important issues in 3D CD methods. Finally, we present concluding remarks in algorithmic aspects of 3D CD.

  15. RT3D tutorials for GMS users

    SciTech Connect

    Clement, T.P.; Jones, N.L.

    1998-02-01

    RT3D (Reactive Transport in 3-Dimensions) is a computer code that solves coupled partial differential equations that describe reactive-flow and transport of multiple mobile and/or immobile species in a three dimensional saturated porous media. RT3D was developed from the single-species transport code, MT3D (DoD-1.5, 1997 version). As with MT3D, RT3D also uses the USGS groundwater flow model MODFLOW for computing spatial and temporal variations in groundwater head distribution. This report presents a set of tutorial problems that are designed to illustrate how RT3D simulations can be performed within the Department of Defense Groundwater Modeling System (GMS). GMS serves as a pre- and post-processing interface for RT3D. GMS can be used to define all the input files needed by RT3D code, and later the code can be launched from within GMS and run as a separate application. Once the RT3D simulation is completed, the solution can be imported to GMS for graphical post-processing. RT3D v1.0 supports several reaction packages that can be used for simulating different types of reactive contaminants. Each of the tutorials, described below, provides training on a different RT3D reaction package. Each reaction package has different input requirements, and the tutorials are designed to describe these differences. Furthermore, the tutorials illustrate the various options available in GMS for graphical post-processing of RT3D results. Users are strongly encouraged to complete the tutorials before attempting to use RT3D and GMS on a routine basis.

  16. Externally predictive quantitative modeling of supercooled liquid vapor pressure of polychlorinated-naphthalenes through electron-correlation based quantum-mechanical descriptors.

    PubMed

    Vikas; Chayawan

    2014-01-01

    For predicting physico-chemical properties related to environmental fate of molecules, quantitative structure-property relationships (QSPRs) are valuable tools in environmental chemistry. For developing a QSPR, molecular descriptors computed through quantum-mechanical methods are generally employed. The accuracy of a quantum-mechanical method, however, rests on the amount of electron-correlation estimated by the method. In this work, single-descriptor QSPRs for supercooled liquid vapor pressure of chloronaphthalenes and polychlorinated-naphthalenes are developed using molecular descriptors based on the electron-correlation contribution of the quantum-mechanical descriptor. The quantum-mechanical descriptors for which the electron-correlation contribution is analyzed include total-energy, mean polarizability, dipole moment, frontier orbital (HOMO/LUMO) energy, and density-functional theory (DFT) based descriptors, namely, absolute electronegativity, chemical hardness, and electrophilicity index. A total of 40 single-descriptor QSPRs were developed using molecular descriptors computed with advanced semi-empirical (SE) methods, namely, RM1, PM7, and ab intio methods, namely, Hartree-Fock and DFT. The developed QSPRs are validated using state-of-the-art external validation procedures employing an external prediction set. From the comparison of external predictivity of the models, it is observed that the single-descriptor QSPRs developed using total energy and correlation energy are found to be far more robust and predictive than those developed using commonly employed descriptors such as HOMO/LUMO energy and dipole moment. The work proposes that if real external predictivity of a QSPR model is desired to be explored, particularly, in terms of intra-molecular interactions, correlation-energy serves as a more appropriate descriptor than the polarizability. However, for developing QSPRs, computationally inexpensive advanced SE methods such as PM7 can be more reliable than

  17. 3D measurement for rapid prototyping

    NASA Astrophysics Data System (ADS)

    Albrecht, Peter; Lilienblum, Tilo; Sommerkorn, Gerd; Michaelis, Bernd

    1996-08-01

    Optical 3-D measurement is an interesting approach for rapid prototyping. On one hand it's necessary to get the 3-D data of an object and on the other hand it's necessary to check the manufactured object (quality checking). Optical 3-D measurement can realize both. Classical 3-D measurement procedures based on photogrammetry cause systematic errors at strongly curved surfaces or steps in surfaces. One possibility to reduce these errors is to calculate the 3-D coordinates from several successively taken images. Thus it's possible to get higher spatial resolution and to reduce the systematic errors at 'problem surfaces.' Another possibility is to process the measurement values by neural networks. A modified associative memory smoothes and corrects the calculated 3-D coordinates using a-priori knowledge about the measurement object.

  18. Application of Fourier descriptors and neural network to classification underground images

    NASA Astrophysics Data System (ADS)

    Tolstoy, Leonid; Parsiani, Hamed; Ortiz, Jorge

    2003-03-01

    This paper presents an application of Fourier Descriptors and Neural Network for the recognition of archeological artifacts in Ground Penetrating Radar (GPR) images of a surveyed site. Multiple 2-D GPR images of a site are made available by NASA-SSC center. The buried artifacts in these images appear in the form of parabolas which are the results of radar backscatter from the artifacts. The Fourier Descriptors of an image are applied as inputs to a feed-forward backpropagation Neural Network Classifier (NNC). The NNC algorithm was trained to recognize parabola-like shapes from non-parabola shapes in the sub-surface images. The procedure consisted of removing background noise using a suitable threshold filter, locating the separate shapes in the image using N8(p) connectivity algorithm, calculating a short sequence of Fourier Descriptors (FD) of each isolated shape, and finally classifying parabola/no-parabola using Neural Network applied to the FDs. The results are images with recognized parabolas which indicate the presence of buried artifacts. As a useful feature to archeologists, a 3-D Visualization of the complete survey area is produced using C++ and Visualization Tool Kit. The Algorithms for removing the background noise, thresholding, calculating the Fourier Descriptors, and obtaining a classification using a Neural Network were developed using Matlab.

  19. Photorefractive Polymers for Updateable 3D Displays

    DTIC Science & Technology

    2010-02-24

    Final Performance Report 3. DATES COVERED (From - To) 01-01-2007 to 11-30-2009 4. TITLE AND SUBTITLE Photorefractive Polymers for Updateable 3D ...ABSTRACT During the tenure of this project a large area updateable 3D color display has been developed for the first time using a new co-polymer...photorefractive polymers have been demonstrated. Moreover, a 6 inch × 6 inch sample was fabricated demonstrating the feasibility of making large area 3D

  20. 3D Microperfusion Model of ADPKD

    DTIC Science & Technology

    2015-10-01

    Stratasys 3D printer . PDMS was cast in the negative molds in order to create permanent biocompatible plastic masters (SmoothCast 310). All goals of task...1 AWARD NUMBER: W81XWH-14-1-0304 TITLE: 3D Microperfusion Model of ADPKD PRINCIPAL INVESTIGATOR: David L. Kaplan CONTRACTING ORGANIZATION...ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE Annual Report 3. DATES COVERED 15 Sep 2014 - 14 Sep 2015 4. TITLE AND SUBTITLE 3D

  1. 3D carotid plaque MR Imaging

    PubMed Central

    Parker, Dennis L.

    2015-01-01

    SYNOPSIS There has been significant progress made in 3D carotid plaque magnetic resonance imaging techniques in recent years. 3D plaque imaging clearly represents the future in clinical use. With effective flow suppression techniques, choices of different contrast weighting acquisitions, and time-efficient imaging approaches, 3D plaque imaging offers flexible imaging plane and view angle analysis, large coverage, multi-vascular beds capability, and even can be used in fast screening. PMID:26610656

  2. 3-D Extensions for Trustworthy Systems

    DTIC Science & Technology

    2011-01-01

    3- D Extensions for Trustworthy Systems (Invited Paper) Ted Huffmire∗, Timothy Levin∗, Cynthia Irvine∗, Ryan Kastner† and Timothy Sherwood...address these problems, we propose an approach to trustworthy system development based on 3- D integration, an emerging chip fabrication technique in...which two or more integrated circuit dies are fabricated individually and then combined into a single stack using vertical conductive posts. With 3- D

  3. Hardware Trust Implications of 3-D Integration

    DTIC Science & Technology

    2010-12-01

    enhancing a commod- ity processor with a variety of security functions. This paper examines the 3-D design approach and provides an analysis concluding...of key components. The question addressed by this paper is, “Can a 3-D control plane provide useful secure services when it is conjoined with an...untrust- worthy computation plane?” Design-level investigation of this question yields a definite yes. This paper explores 3- D applications and their

  4. Digital holography and 3-D imaging.

    PubMed

    Banerjee, Partha; Barbastathis, George; Kim, Myung; Kukhtarev, Nickolai

    2011-03-01

    This feature issue on Digital Holography and 3-D Imaging comprises 15 papers on digital holographic techniques and applications, computer-generated holography and encryption techniques, and 3-D display. It is hoped that future work in the area leads to innovative applications of digital holography and 3-D imaging to biology and sensing, and to the development of novel nonlinear dynamic digital holographic techniques.

  5. Dimensional accuracy of 3D printed vertebra

    NASA Astrophysics Data System (ADS)

    Ogden, Kent; Ordway, Nathaniel; Diallo, Dalanda; Tillapaugh-Fay, Gwen; Aslan, Can

    2014-03-01

    3D printer applications in the biomedical sciences and medical imaging are expanding and will have an increasing impact on the practice of medicine. Orthopedic and reconstructive surgery has been an obvious area for development of 3D printer applications as the segmentation of bony anatomy to generate printable models is relatively straightforward. There are important issues that should be addressed when using 3D printed models for applications that may affect patient care; in particular the dimensional accuracy of the printed parts needs to be high to avoid poor decisions being made prior to surgery or therapeutic procedures. In this work, the dimensional accuracy of 3D printed vertebral bodies derived from CT data for a cadaver spine is compared with direct measurements on the ex-vivo vertebra and with measurements made on the 3D rendered vertebra using commercial 3D image processing software. The vertebra was printed on a consumer grade 3D printer using an additive print process using PLA (polylactic acid) filament. Measurements were made for 15 different anatomic features of the vertebral body, including vertebral body height, endplate width and depth, pedicle height and width, and spinal canal width and depth, among others. It is shown that for the segmentation and printing process used, the results of measurements made on the 3D printed vertebral body are substantially the same as those produced by direct measurement on the vertebra and measurements made on the 3D rendered vertebra.

  6. Usefulness of descriptors in phenotyping germplasm collections

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A large number of crop germplasm collections are maintained within the U.S. National Plant Germplasm System (NPGS). For each of these crop collections, Crop Germplasm committees (CGC), crop curators, and collection staff have established extensive lists of descriptors or phenotypic traits by which t...

  7. Non-isothermal 3D SDPD Simulations

    NASA Astrophysics Data System (ADS)

    Yang, Jun; Potami, Raffaele; Gatsonis, Nikolaos

    2012-11-01

    The study of fluids at micro and nanoscale requires new modeling and computational approaches. Smooth Particle Dissipative Dynamics (SDPD) is a mesh-free method that provides a bridge between the continuum equations of hydrodynamics embedded in the Smooth Particle Hydrodynamics approach and the molecular nature embedded in the DPD approach. SDPD is thermodynamically consistent, does not rely on arbitrary coefficients for its thermostat, involves realistic transport coefficients, and includes fluctuation terms. SDPD is implemented in our work for arbitrary 3D geometries with a methodology to model solid wall boundary conditions. We present simulations for isothermal flows for verification of our approach. The entropy equation is implemented with a velocity-entropy Verlet integration algorithm Flows with heat transfer are simulated for verification of the SDPD. We present also the self-diffusion coefficient derived from SDPD simulations for gases and liquids. Results show the scale dependence of self-diffusion coefficient on SDPD particle size. Computational Mathematics Program of the Air Force Office of Scientific Research under grant/contract number FA9550-06-1-0236.

  8. FastScript3D - A Companion to Java 3D

    NASA Technical Reports Server (NTRS)

    Koenig, Patti

    2005-01-01

    FastScript3D is a computer program, written in the Java 3D(TM) programming language, that establishes an alternative language that helps users who lack expertise in Java 3D to use Java 3D for constructing three-dimensional (3D)-appearing graphics. The FastScript3D language provides a set of simple, intuitive, one-line text-string commands for creating, controlling, and animating 3D models. The first word in a string is the name of a command; the rest of the string contains the data arguments for the command. The commands can also be used as an aid to learning Java 3D. Developers can extend the language by adding custom text-string commands. The commands can define new 3D objects or load representations of 3D objects from files in formats compatible with such other software systems as X3D. The text strings can be easily integrated into other languages. FastScript3D facilitates communication between scripting languages [which enable programming of hyper-text markup language (HTML) documents to interact with users] and Java 3D. The FastScript3D language can be extended and customized on both the scripting side and the Java 3D side.

  9. Image-Based Airborne LiDAR Point Cloud Encoding for 3d Building Model Retrieval

    NASA Astrophysics Data System (ADS)

    Chen, Yi-Chen; Lin, Chao-Hung

    2016-06-01

    With the development of Web 2.0 and cyber city modeling, an increasing number of 3D models have been available on web-based model-sharing platforms with many applications such as navigation, urban planning, and virtual reality. Based on the concept of data reuse, a 3D model retrieval system is proposed to retrieve building models similar to a user-specified query. The basic idea behind this system is to reuse these existing 3D building models instead of reconstruction from point clouds. To efficiently retrieve models, the models in databases are compactly encoded by using a shape descriptor generally. However, most of the geometric descriptors in related works are applied to polygonal models. In this study, the input query of the model retrieval system is a point cloud acquired by Light Detection and Ranging (LiDAR) systems because of the efficient scene scanning and spatial information collection. Using Point clouds with sparse, noisy, and incomplete sampling as input queries is more difficult than that by using 3D models. Because that the building roof is more informative than other parts in the airborne LiDAR point cloud, an image-based approach is proposed to encode both point clouds from input queries and 3D models in databases. The main goal of data encoding is that the models in the database and input point clouds can be consistently encoded. Firstly, top-view depth images of buildings are generated to represent the geometry surface of a building roof. Secondly, geometric features are extracted from depth images based on height, edge and plane of building. Finally, descriptors can be extracted by spatial histograms and used in 3D model retrieval system. For data retrieval, the models are retrieved by matching the encoding coefficients of point clouds and building models. In experiments, a database including about 900,000 3D models collected from the Internet is used for evaluation of data retrieval. The results of the proposed method show a clear superiority

  10. 3D ultrafast ultrasound imaging in vivo.

    PubMed

    Provost, Jean; Papadacci, Clement; Arango, Juan Esteban; Imbault, Marion; Fink, Mathias; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

    2014-10-07

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra--and inter-observer variability.

  11. 3D ultrafast ultrasound imaging in vivo

    NASA Astrophysics Data System (ADS)

    Provost, Jean; Papadacci, Clement; Esteban Arango, Juan; Imbault, Marion; Fink, Mathias; Gennisson, Jean-Luc; Tanter, Mickael; Pernot, Mathieu

    2014-10-01

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra—and inter-observer variability.

  12. An aerial 3D printing test mission

    NASA Astrophysics Data System (ADS)

    Hirsch, Michael; McGuire, Thomas; Parsons, Michael; Leake, Skye; Straub, Jeremy

    2016-05-01

    This paper provides an overview of an aerial 3D printing technology, its development and its testing. This technology is potentially useful in its own right. In addition, this work advances the development of a related in-space 3D printing technology. A series of aerial 3D printing test missions, used to test the aerial printing technology, are discussed. Through completing these test missions, the design for an in-space 3D printer may be advanced. The current design for the in-space 3D printer involves focusing thermal energy to heat an extrusion head and allow for the extrusion of molten print material. Plastics can be used as well as composites including metal, allowing for the extrusion of conductive material. A variety of experiments will be used to test this initial 3D printer design. High altitude balloons will be used to test the effects of microgravity on 3D printing, as well as parabolic flight tests. Zero pressure balloons can be used to test the effect of long 3D printing missions subjected to low temperatures. Vacuum chambers will be used to test 3D printing in a vacuum environment. The results will be used to adapt a current prototype of an in-space 3D printer. Then, a small scale prototype can be sent into low-Earth orbit as a 3-U cube satellite. With the ability to 3D print in space demonstrated, future missions can launch production hardware through which the sustainability and durability of structures in space will be greatly improved.

  13. Systems biology in 3D space--enter the morphome.

    PubMed

    Lucocq, John M; Mayhew, Terry M; Schwab, Yannick; Steyer, Anna M; Hacker, Christian

    2015-02-01

    Systems-based understanding of living organisms depends on acquiring huge datasets from arrays of genes, transcripts, proteins, and lipids. These data, referred to as 'omes', are assembled using 'omics' methodologies. Currently a comprehensive, quantitative view of cellular and organellar systems in 3D space at nanoscale/molecular resolution is missing. We introduce here the term 'morphome' for the distribution of living matter within a 3D biological system, and 'morphomics' for methods of collecting 3D data systematically and quantitatively. A sampling-based approach termed stereology currently provides rapid, precise, and minimally biased morphomics. We propose that stereology solves the 'big data' problem posed by emerging wide-scale electron microscopy (EM) and can establish quantitative links between the newer nanoimaging platforms such as electron tomography, cryo-EM, and correlative microscopy.

  14. 3D RISM theory with fast reciprocal-space electrostatics

    SciTech Connect

    Heil, Jochen; Kast, Stefan M.

    2015-03-21

    The calculation of electrostatic solute-solvent interactions in 3D RISM (“three-dimensional reference interaction site model”) integral equation theory is recast in a form that allows for a computational treatment analogous to the “particle-mesh Ewald” formalism as used for molecular simulations. In addition, relations that connect 3D RISM correlation functions and interaction potentials with thermodynamic quantities such as the chemical potential and average solute-solvent interaction energy are reformulated in a way that calculations of expensive real-space electrostatic terms on the 3D grid are completely avoided. These methodical enhancements allow for both, a significant speedup particularly for large solute systems and a smoother convergence of predicted thermodynamic quantities with respect to box size, as illustrated for several benchmark systems.

  15. Algorithms for Haptic Rendering of 3D Objects

    NASA Technical Reports Server (NTRS)

    Basdogan, Cagatay; Ho, Chih-Hao; Srinavasan, Mandayam

    2003-01-01

    Algorithms have been developed to provide haptic rendering of three-dimensional (3D) objects in virtual (that is, computationally simulated) environments. The goal of haptic rendering is to generate tactual displays of the shapes, hardnesses, surface textures, and frictional properties of 3D objects in real time. Haptic rendering is a major element of the emerging field of computer haptics, which invites comparison with computer graphics. We have already seen various applications of computer haptics in the areas of medicine (surgical simulation, telemedicine, haptic user interfaces for blind people, and rehabilitation of patients with neurological disorders), entertainment (3D painting, character animation, morphing, and sculpting), mechanical design (path planning and assembly sequencing), and scientific visualization (geophysical data analysis and molecular manipulation).

  16. Integration of real-time 3D image acquisition and multiview 3D display

    NASA Astrophysics Data System (ADS)

    Zhang, Zhaoxing; Geng, Zheng; Li, Tuotuo; Li, Wei; Wang, Jingyi; Liu, Yongchun

    2014-03-01

    Seamless integration of 3D acquisition and 3D display systems offers enhanced experience in 3D visualization of the real world objects or scenes. The vivid representation of captured 3D objects displayed on a glasses-free 3D display screen could bring the realistic viewing experience to viewers as if they are viewing real-world scene. Although the technologies in 3D acquisition and 3D display have advanced rapidly in recent years, effort is lacking in studying the seamless integration of these two different aspects of 3D technologies. In this paper, we describe our recent progress on integrating a light-field 3D acquisition system and an autostereoscopic multiview 3D display for real-time light field capture and display. This paper focuses on both the architecture design and the implementation of the hardware and the software of this integrated 3D system. A prototype of the integrated 3D system is built to demonstrate the real-time 3D acquisition and 3D display capability of our proposed system.

  17. Immersive 3D Geovisualization in Higher Education

    ERIC Educational Resources Information Center

    Philips, Andrea; Walz, Ariane; Bergner, Andreas; Graeff, Thomas; Heistermann, Maik; Kienzler, Sarah; Korup, Oliver; Lipp, Torsten; Schwanghart, Wolfgang; Zeilinger, Gerold

    2015-01-01

    In this study, we investigate how immersive 3D geovisualization can be used in higher education. Based on MacEachren and Kraak's geovisualization cube, we examine the usage of immersive 3D geovisualization and its usefulness in a research-based learning module on flood risk, called GEOSimulator. Results of a survey among participating students…

  18. A 3D Geostatistical Mapping Tool

    SciTech Connect

    Weiss, W. W.; Stevenson, Graig; Patel, Ketan; Wang, Jun

    1999-02-09

    This software provides accurate 3D reservoir modeling tools and high quality 3D graphics for PC platforms enabling engineers and geologists to better comprehend reservoirs and consequently improve their decisions. The mapping algorithms are fractals, kriging, sequential guassian simulation, and three nearest neighbor methods.

  19. 3D Printing. What's the Harm?

    ERIC Educational Resources Information Center

    Love, Tyler S.; Roy, Ken

    2016-01-01

    Health concerns from 3D printing were first documented by Stephens, Azimi, Orch, and Ramos (2013), who found that commercially available 3D printers were producing hazardous levels of ultrafine particles (UFPs) and volatile organic compounds (VOCs) when plastic materials were melted through the extruder. UFPs are particles less than 100 nanometers…

  20. 3D elastic control for mobile devices.

    PubMed

    Hachet, Martin; Pouderoux, Joachim; Guitton, Pascal

    2008-01-01

    To increase the input space of mobile devices, the authors developed a proof-of-concept 3D elastic controller that easily adapts to mobile devices. This embedded device improves the completion of high-level interaction tasks such as visualization of large documents and navigation in 3D environments. It also opens new directions for tomorrow's mobile applications.

  1. Infrastructure for 3D Imaging Test Bed

    DTIC Science & Technology

    2007-05-11

    analysis. (c.) Real time detection & analysis of human gait: using a video camera we capture walking human silhouette for pattern modeling and gait ... analysis . Fig. 5 shows the scanning result result that is fed into a Geo-magic software tool for 3D meshing. Fig. 5: 3D scanning result In

  2. Wow! 3D Content Awakens the Classroom

    ERIC Educational Resources Information Center

    Gordon, Dan

    2010-01-01

    From her first encounter with stereoscopic 3D technology designed for classroom instruction, Megan Timme, principal at Hamilton Park Pacesetter Magnet School in Dallas, sensed it could be transformative. Last spring, when she began pilot-testing 3D content in her third-, fourth- and fifth-grade classrooms, Timme wasn't disappointed. Students…

  3. Stereo 3-D Vision in Teaching Physics

    ERIC Educational Resources Information Center

    Zabunov, Svetoslav

    2012-01-01

    Stereo 3-D vision is a technology used to present images on a flat surface (screen, paper, etc.) and at the same time to create the notion of three-dimensional spatial perception of the viewed scene. A great number of physical processes are much better understood when viewed in stereo 3-D vision compared to standard flat 2-D presentation. The…

  4. Pathways for Learning from 3D Technology

    ERIC Educational Resources Information Center

    Carrier, L. Mark; Rab, Saira S.; Rosen, Larry D.; Vasquez, Ludivina; Cheever, Nancy A.

    2012-01-01

    The purpose of this study was to find out if 3D stereoscopic presentation of information in a movie format changes a viewer's experience of the movie content. Four possible pathways from 3D presentation to memory and learning were considered: a direct connection based on cognitive neuroscience research; a connection through "immersion"…

  5. 3D, or Not to Be?

    ERIC Educational Resources Information Center

    Norbury, Keith

    2012-01-01

    It may be too soon for students to be showing up for class with popcorn and gummy bears, but technology similar to that behind the 3D blockbuster movie "Avatar" is slowly finding its way into college classrooms. 3D classroom projectors are taking students on fantastic voyages inside the human body, to the ruins of ancient Greece--even to faraway…

  6. Static & Dynamic Response of 3D Solids

    SciTech Connect

    Lin, Jerry

    1996-07-15

    NIKE3D is a large deformations 3D finite element code used to obtain the resulting displacements and stresses from multi-body static and