The Experts below are selected from a list of 60762 Experts worldwide ranked by ideXlab platform
Holger Gohlke - One of the best experts on this subject based on the ideXlab platform.
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F/G Region Rigidity is Inversely Correlated to Substrate Promiscuity of Human CYP Isoforms Involved in Metabolism
'American Chemical Society (ACS)', 2021Co-Authors: Daniel Becker, Prasad V. Bharatam, Holger GohlkeAbstract:Of 57 human cytochrome P450 (CYP) enzymes, 12 metabolize 90% of xenobiotics. To our knowledge, no study has addressed the relation between enzyme dynamics and substrate promiscuity for more than three CYPs. Here, we show by Constraint dilution simulations with the Constraint Network Analysis for the 12 isoforms that structural rigidity of the F/G region is significantly inversely correlated to the enzymes’ substrate promiscuity. This highlights the functional importance of structural dynamics of the substrate tunnel
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Constraint Network analysis cna a python software package for efficiently linking biomacromolecular structure flexibility thermo stability and function
Journal of Chemical Information and Modeling, 2013Co-Authors: Christopher Pfleger, Prakash Chandra Rathi, Doris L Klein, Sebastian Radestock, Holger GohlkeAbstract:For deriving maximal advantage from information on biomacromolecular flexibility and rigidity, results from rigidity analyses must be linked to biologically relevant characteristics of a structure. Here, we describe the Python-based software package Constraint Network Analysis (CNA) developed for this task. CNA functions as a front- and backend to the graph-based rigidity analysis software FIRST. CNA goes beyond the mere identification of flexible and rigid regions in a biomacromolecule in that it (I) provides a refined modeling of thermal unfolding simulations that also considers the temperature-dependence of hydrophobic tethers, (II) allows performing rigidity analyses on ensembles of Network topologies, either generated from structural ensembles or by using the concept of fuzzy noncovalent Constraints, and (III) computes a set of global and local indices for quantifying biomacromolecular stability. This leads to more robust results from rigidity analyses and extends the application domain of rigidity a...
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Constraint Network analysis cna a python software package for efficiently linking biomacromolecular structure flexibility thermo stability and function
Journal of Chemical Information and Modeling, 2013Co-Authors: Christopher Pfleger, Prakash Chandra Rathi, Doris L Klein, Sebastian Radestock, Holger GohlkeAbstract:For deriving maximal advantage from information on biomacromolecular flexibility and rigidity, results from rigidity analyses must be linked to biologically relevant characteristics of a structure. Here, we describe the Python-based software package Constraint Network Analysis (CNA) developed for this task. CNA functions as a front- and backend to the graph-based rigidity analysis software FIRST. CNA goes beyond the mere identification of flexible and rigid regions in a biomacromolecule in that it (I) provides a refined modeling of thermal unfolding simulations that also considers the temperature-dependence of hydrophobic tethers, (II) allows performing rigidity analyses on ensembles of Network topologies, either generated from structural ensembles or by using the concept of fuzzy noncovalent Constraints, and (III) computes a set of global and local indices for quantifying biomacromolecular stability. This leads to more robust results from rigidity analyses and extends the application domain of rigidity analyses in that phase transition points ("melting points") and unfolding nuclei ("structural weak spots") are determined automatically. Furthermore, CNA robustly handles small-molecule ligands in general. Such advancements are important for applying rigidity analysis to data-driven protein engineering and for estimating the influence of ligand molecules on biomacromolecular stability. CNA maintains the efficiency of FIRST such that the analysis of a single protein structure takes a few seconds for systems of several hundred residues on a single core. These features make CNA an interesting tool for linking biomacromolecular structure, flexibility, (thermo-)stability, and function. CNA is available from http://cpclab.uni-duesseldorf.de/software for nonprofit organizations.
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protein rigidity and thermophilic adaptation
Proteins, 2011Co-Authors: Sebastian Radestock, Holger GohlkeAbstract:We probe the hypothesis of corresponding states, according to which homologues from mesophilic and thermophilic organisms are in corresponding states of similar rigidity and flexibility at their respective optimal temperatures. For this, the local distribution of flexible and rigid regions in 19 pairs of homologous proteins from meso- and thermophilic organisms is analyzed and related to activity characteristics of the enzymes by Constraint Network analysis (CNA). Two pairs of enzymes are considered in more detail: 3-isopropylmalate dehydrogenase and thermolysin-like protease. By comparing microscopic stability features of homologues with the help of stability maps, introduced for the first time, we show that adaptive mutations in enzymes from thermophilic organisms maintain the balance between overall rigidity, important for thermostability, and local flexibility, important for activity, at the appropriate working temperature. Thermophilic adaptation in general leads to an increase of structural rigidity but conserves the distribution of functionally important flexible regions between homologues. This finding provides direct evidence for the hypothesis of corresponding states. CNA thereby implicitly captures and unifies many different mechanisms that contribute to increased thermostability and to activity at high temperatures. This allows to qualitatively relate changes in the flexibility of active site regions, induced either by a temperature change or by the introduction of mutations, to experimentally observed losses of the enzyme function. As for applications, the results demonstrate that exploiting the principle of corresponding states not only allows for successful thermostability optimization but also for guiding experiments in order to improve enzyme activity in protein engineering. Proteins 2011. © 2010 Wiley-Liss, Inc.
Christopher Pfleger - One of the best experts on this subject based on the ideXlab platform.
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Constraint Network analysis cna a python software package for efficiently linking biomacromolecular structure flexibility thermo stability and function
Journal of Chemical Information and Modeling, 2013Co-Authors: Christopher Pfleger, Prakash Chandra Rathi, Doris L Klein, Sebastian Radestock, Holger GohlkeAbstract:For deriving maximal advantage from information on biomacromolecular flexibility and rigidity, results from rigidity analyses must be linked to biologically relevant characteristics of a structure. Here, we describe the Python-based software package Constraint Network Analysis (CNA) developed for this task. CNA functions as a front- and backend to the graph-based rigidity analysis software FIRST. CNA goes beyond the mere identification of flexible and rigid regions in a biomacromolecule in that it (I) provides a refined modeling of thermal unfolding simulations that also considers the temperature-dependence of hydrophobic tethers, (II) allows performing rigidity analyses on ensembles of Network topologies, either generated from structural ensembles or by using the concept of fuzzy noncovalent Constraints, and (III) computes a set of global and local indices for quantifying biomacromolecular stability. This leads to more robust results from rigidity analyses and extends the application domain of rigidity a...
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Constraint Network analysis cna a python software package for efficiently linking biomacromolecular structure flexibility thermo stability and function
Journal of Chemical Information and Modeling, 2013Co-Authors: Christopher Pfleger, Prakash Chandra Rathi, Doris L Klein, Sebastian Radestock, Holger GohlkeAbstract:For deriving maximal advantage from information on biomacromolecular flexibility and rigidity, results from rigidity analyses must be linked to biologically relevant characteristics of a structure. Here, we describe the Python-based software package Constraint Network Analysis (CNA) developed for this task. CNA functions as a front- and backend to the graph-based rigidity analysis software FIRST. CNA goes beyond the mere identification of flexible and rigid regions in a biomacromolecule in that it (I) provides a refined modeling of thermal unfolding simulations that also considers the temperature-dependence of hydrophobic tethers, (II) allows performing rigidity analyses on ensembles of Network topologies, either generated from structural ensembles or by using the concept of fuzzy noncovalent Constraints, and (III) computes a set of global and local indices for quantifying biomacromolecular stability. This leads to more robust results from rigidity analyses and extends the application domain of rigidity analyses in that phase transition points ("melting points") and unfolding nuclei ("structural weak spots") are determined automatically. Furthermore, CNA robustly handles small-molecule ligands in general. Such advancements are important for applying rigidity analysis to data-driven protein engineering and for estimating the influence of ligand molecules on biomacromolecular stability. CNA maintains the efficiency of FIRST such that the analysis of a single protein structure takes a few seconds for systems of several hundred residues on a single core. These features make CNA an interesting tool for linking biomacromolecular structure, flexibility, (thermo-)stability, and function. CNA is available from http://cpclab.uni-duesseldorf.de/software for nonprofit organizations.
Homero Mauricio Schneider - One of the best experts on this subject based on the ideXlab platform.
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Estabelecendo um processo de customização livre de retrocessos para famílias de produtos
2017Co-Authors: Homero Mauricio SchneiderAbstract:Resumo: Um conceito chave na área de customização em massa é o de família de produtos. Embora o projeto de uma família de produtos é uma tarefa difícil e desafiadora, derivar os membros da família de produtos para atender os requisitos de clientes individuais pode ser uma tarefa de design rotineira. Neste trabalho, propomos uma abordagem formal para modelar o processo de customização de famílias de produtos, que alcançar este objetivo. De fato, construímos uma teoria para a customização de famílias de produtos. Esta abordagem é baseada em uma estrutura de conhecimento para a representação de famílias de produtos que combina uma estrutura de produto genérica e uma rede de restrições estendida com funções de design. O método para derivar os membros da família de produtos é um processo de instanciação com duas fases. Primeiramente, uma solução para o modelo de rede de restrição consistente com os requisitos do cliente é encontrada. Em seguida, esta solução é utilizada para transformar a estrutura de produto genérica em uma estrutura especifica que corresponde a um membro da família de produtos. Neste trabalho, provamos que, se o modelo de rede de restrição estendida com funções de design satisfaz algumas condições de modelagem, então encontrar soluções se torna um processo livre de retrocessos. Embora existam outros trabalhos na literatura que também afirmam ser livre de retrocessos, um fato notável sobre a nossa abordagem é que conseguimos isso através da introdução de conhecimento sobre a família de produtos, em vez de recorrer ao poder computacional e pré-processamento como naquelas abordagens. Outro aspecto notável da nossa abordagem é que os componentes podem ser projetados como parte do processo de personalização através das funções de design. Isto implica que é possível dispor de um processo de customização eficiente sem comprometer a flexibilidade da família de produtos. Na conclusão deste trabalho, argumentamos que a nossa abordagem pode lidar com problemas de customização que estão fora da área de configuração de produtos. Dois apêndices também são adicionados à tese. Um deles é uma modelagem completa de uma família de produtos Chave de Transferência Automática (ATS) baseado em nossa abordagem. Este exemplo é usado no corpo principal da tese para ilustrar os conceitos que estão sendo introduzidos. A outra é uma implementação computacional do primeiro estágio do processo de customização da família de produtos ATS.Abstract: Product family is a key concept is the area of mass customisation. Although the design of a product family is a difficult and challenging task, to derive members of the product family to meet the requirements of individual customers can be a routine design task. In this work, we propose a formal approach to model the customisation of product families that achieves this goal. In fact, we are setting up a theory for the customization of product families. This approach is based on a knowledge framework for the representation of product families, which combines a generic product structure and a Constraint Network extended with design functions. The method for deriving members of the product family is a two-stage instantiation process. First, a solution to the Constraint Network model consistent with the customer requirements is found. Next, this solution is used to transform the generic product structure into a specific structure that corresponds to a member of the product family. In this work, we prove that if the Constraint Network model extended with design functions satisfies a few modelling conditions, then to find solutions become a backtrack-free process. Although there are other works in the literature that also claim to be backtrack-free, a remarkable fact about our approach is that we achieve this by the introduction of knowledge about the product family, instead of resorting to computational power and pre-processing as in those approaches. Another remarkable aspect of our approach is that components can be designed as part of the customisation process using the design functions. This implies that it is possible to have an efficient customisation process without compromising the flexibility of the product family. In the conclusion of this work, we argue that our approach can deal with customisation problems outside the product configuration area. Two appendixes are also added to the thesis. One is a compete modelling of the Automatic Transfer Switch (ATS) product family using our approach. This example is used in the main body of the thesis to illustrate the concepts that are being introduced. The other one is the computational implementation of the first-stage customisation process of the ATS product Family
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Estabelecendo um processo de customização livre de retrocessos para famílias de produtos
Universidade Estadual de Campinas . Faculdade de Engenharia Elétrica e de Computação, 2014Co-Authors: Homero Mauricio SchneiderAbstract:Um conceito chave na área de customização em massa é o de família de produtos. Embora o projeto de uma família de produtos é uma tarefa difícil e desafiadora, derivar os membros da família de produtos para atender os requisitos de clientes individuais pode ser uma tarefa de design rotineira. Neste trabalho, propomos uma abordagem formal para modelar o processo de customização de famílias de produtos, que alcançar este objetivo. De fato, construímos uma teoria para a customização de famílias de produtos. Esta abordagem é baseada em uma estrutura de conhecimento para a representação de famílias de produtos que combina uma estrutura de produto genérica e uma rede de restrições estendida com funções de design. O método para derivar os membros da família de produtos é um processo de instanciação com duas fases. Primeiramente, uma solução para o modelo de rede de restrição consistente com os requisitos do cliente é encontrada. Em seguida, esta solução é utilizada para transformar a estrutura de produto genérica em uma estrutura especifica que corresponde a um membro da família de produtos. Neste trabalho, provamos que, se o modelo de rede de restrição estendida com funções de design satisfaz algumas condições de modelagem, então encontrar soluções se torna um processo livre de retrocessos. Embora existam outros trabalhos na literatura que também afirmam ser livre de retrocessos, um fato notável sobre a nossa abordagem é que conseguimos isso através da introdução de conhecimento sobre a família de produtos, em vez de recorrer ao poder computacional e pré-processamento como naquelas abordagens. Outro aspecto notável da nossa abordagem é que os componentes podem ser projetados como parte do processo de personalização através das funções de design. Isto implica que é possível dispor de um processo de customização eficiente sem comprometer a flexibilidade da família de produtos. Na conclusão deste trabalho, argumentamos que a nossa abordagem pode lidar com problemas de customização que estão fora da área de configuração de produtos. Dois apêndices também são adicionados à tese. Um deles é uma modelagem completa de uma família de produtos Chave de Transferência Automática (ATS) baseado em nossa abordagem. Este exemplo é usado no corpo principal da tese para ilustrar os conceitos que estão sendo introduzidos. A outra é uma implementação computacional do primeiro estágio do processo de customização da família de produtos ATS.Product family is a key concept is the area of mass customisation. Although the design of a product family is a difficult and challenging task, to derive members of the product family to meet the requirements of individual customers can be a routine design task. In this work, we propose a formal approach to model the customisation of product families that achieves this goal. In fact, we are setting up a theory for the customization of product families. This approach is based on a knowledge framework for the representation of product families, which combines a generic product structure and a Constraint Network extended with design functions. The method for deriving members of the product family is a two-stage instantiation process. First, a solution to the Constraint Network model consistent with the customer requirements is found. Next, this solution is used to transform the generic product structure into a specific structure that corresponds to a member of the product family. In this work, we prove that if the Constraint Network model extended with design functions satisfies a few modelling conditions, then to find solutions become a backtrack-free process. Although there are other works in the literature that also claim to be backtrack-free, a remarkable fact about our approach is that we achieve this by the introduction of knowledge about the product family, instead of resorting to computational power and pre-processing as in those approaches. Another remarkable aspect of our approach is that components can be designed as part of the customisation process using the design functions. This implies that it is possible to have an efficient customisation process without compromising the flexibility of the product family. In the conclusion of this work, we argue that our approach can deal with customisation problems outside the product configuration area. Two appendixes are also added to the thesis. One is a compete modelling of the Automatic Transfer Switch (ATS) product family using our approach. This example is used in the main body of the thesis to illustrate the concepts that are being introduced. The other one is the computational implementation of the first-stage customisation process of the ATS product Family
Christopher C Yang - One of the best experts on this subject based on the ideXlab platform.
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an associate Constraint Network approach to extract multi lingual information for crime analysis
Decision Support Systems, 2007Co-Authors: Christopher C YangAbstract:International crime and terrorism have drawn increasing attention in recent years. Retrieving relevant information from criminal records and suspect communications is important in combating international crime and terrorism. However, most of this information is written in languages other than English and is stored in various locations. Information sharing between countries therefore presents the challenge of cross-lingual semantic interoperability. In this work, we propose a new approach - the associate Constraint Network - to generate a cross-lingual concept space from a parallel corpus, and benchmark it with a previously developed technique, the Hopfield Network. The associate Constraint Network is a Constraint programming based algorithm, and the problem of generating the cross-lingual concept space is formulated as a Constraint satisfaction problem. Nodes and arcs in an associate Constraint Network represent extracted terms from parallel corpora and their associations. Constraints are defined for the nodes in the associate Constraint Network, and node consistency and Network satisfaction are also defined. Backmarking is developed to search for a feasible solution. Our experimental results show that the associate Constraint Network outperforms the Hopfield Network in precision, recall and efficiency. The cross-lingual concept space that is generated with this method can assist crime analysts to determine the relevance of criminals, crimes, locations and activities in multiple languages, which is information that is not available in traditional thesauri and dictionaries.
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using associate Constraint Network with forward evaluation to overcome cross lingual semantic interoperability challenge for crime information extraction
Systems Man and Cybernetics, 2006Co-Authors: Christopher C Yang, Chihping WeiAbstract:Information extraction is important for crime analysis. Due to the popularity of the Web, information related to crime and terrorism is available in multiple languages. As a result, cross-lingual semantic interoperability is essential when we extract information across multiple languages. In our previous work, we have developed several techniques to generate an automatic cross-lingual thesaurus to support cross-lingual information retrieval based on a parallel corpus collected from the Web. The techniques include Hopfield Network and associate Constraint Network with backmarking. Although these techniques obtain satisfactory performance, they have weaknesses in efficiency, consistency, precision or recall. In this work, we develop a new searching technique, namely forward evaluation, on the basis of our previously developed associate Constraint Network model. We have conducted an experiment and show that the proposed forward evaluation technique outperforms both Hopfield Network and associate Constraint Network with backmarking in terms of precision and recall. In addition, its efficiency is better than Hopfield Network but is not as good as associate Constraint Network with backmarking.
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cross lingual semantics for crime analysis using associate Constraint Network
Intelligence and Security Informatics, 2004Co-Authors: Christopher C YangAbstract:In light of the Bali bombings, East Asia nations rally the international community into a broad-based coalition to support a war against terrorism. The information sharing among different countries provides a challenge for cross-lingual semantic interoperability. In this work, we model the problem as an associate Constraint Network and propagation by backmarking is proposed for creating the cross-lingual concept space. The approach deals with structured as well as unstructured data, addresses relevancy of information, offers the user with associative navigation through the information embedded in the database, enables conduction of multiple languages. Evidence is presented to show that a Constraint programming approach performs well and has the advantage in terms of tractability, ordering and efficiency over the Hopfield Network. The research output consisted of a thesaurus-like, semantic Network knowledge base relied on statistical correlation analysis of the semantics embedded in the documents of English/Chinese parallel corpus.
Sebastian Radestock - One of the best experts on this subject based on the ideXlab platform.
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Constraint Network analysis cna a python software package for efficiently linking biomacromolecular structure flexibility thermo stability and function
Journal of Chemical Information and Modeling, 2013Co-Authors: Christopher Pfleger, Prakash Chandra Rathi, Doris L Klein, Sebastian Radestock, Holger GohlkeAbstract:For deriving maximal advantage from information on biomacromolecular flexibility and rigidity, results from rigidity analyses must be linked to biologically relevant characteristics of a structure. Here, we describe the Python-based software package Constraint Network Analysis (CNA) developed for this task. CNA functions as a front- and backend to the graph-based rigidity analysis software FIRST. CNA goes beyond the mere identification of flexible and rigid regions in a biomacromolecule in that it (I) provides a refined modeling of thermal unfolding simulations that also considers the temperature-dependence of hydrophobic tethers, (II) allows performing rigidity analyses on ensembles of Network topologies, either generated from structural ensembles or by using the concept of fuzzy noncovalent Constraints, and (III) computes a set of global and local indices for quantifying biomacromolecular stability. This leads to more robust results from rigidity analyses and extends the application domain of rigidity a...
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Constraint Network analysis cna a python software package for efficiently linking biomacromolecular structure flexibility thermo stability and function
Journal of Chemical Information and Modeling, 2013Co-Authors: Christopher Pfleger, Prakash Chandra Rathi, Doris L Klein, Sebastian Radestock, Holger GohlkeAbstract:For deriving maximal advantage from information on biomacromolecular flexibility and rigidity, results from rigidity analyses must be linked to biologically relevant characteristics of a structure. Here, we describe the Python-based software package Constraint Network Analysis (CNA) developed for this task. CNA functions as a front- and backend to the graph-based rigidity analysis software FIRST. CNA goes beyond the mere identification of flexible and rigid regions in a biomacromolecule in that it (I) provides a refined modeling of thermal unfolding simulations that also considers the temperature-dependence of hydrophobic tethers, (II) allows performing rigidity analyses on ensembles of Network topologies, either generated from structural ensembles or by using the concept of fuzzy noncovalent Constraints, and (III) computes a set of global and local indices for quantifying biomacromolecular stability. This leads to more robust results from rigidity analyses and extends the application domain of rigidity analyses in that phase transition points ("melting points") and unfolding nuclei ("structural weak spots") are determined automatically. Furthermore, CNA robustly handles small-molecule ligands in general. Such advancements are important for applying rigidity analysis to data-driven protein engineering and for estimating the influence of ligand molecules on biomacromolecular stability. CNA maintains the efficiency of FIRST such that the analysis of a single protein structure takes a few seconds for systems of several hundred residues on a single core. These features make CNA an interesting tool for linking biomacromolecular structure, flexibility, (thermo-)stability, and function. CNA is available from http://cpclab.uni-duesseldorf.de/software for nonprofit organizations.
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protein rigidity and thermophilic adaptation
Proteins, 2011Co-Authors: Sebastian Radestock, Holger GohlkeAbstract:We probe the hypothesis of corresponding states, according to which homologues from mesophilic and thermophilic organisms are in corresponding states of similar rigidity and flexibility at their respective optimal temperatures. For this, the local distribution of flexible and rigid regions in 19 pairs of homologous proteins from meso- and thermophilic organisms is analyzed and related to activity characteristics of the enzymes by Constraint Network analysis (CNA). Two pairs of enzymes are considered in more detail: 3-isopropylmalate dehydrogenase and thermolysin-like protease. By comparing microscopic stability features of homologues with the help of stability maps, introduced for the first time, we show that adaptive mutations in enzymes from thermophilic organisms maintain the balance between overall rigidity, important for thermostability, and local flexibility, important for activity, at the appropriate working temperature. Thermophilic adaptation in general leads to an increase of structural rigidity but conserves the distribution of functionally important flexible regions between homologues. This finding provides direct evidence for the hypothesis of corresponding states. CNA thereby implicitly captures and unifies many different mechanisms that contribute to increased thermostability and to activity at high temperatures. This allows to qualitatively relate changes in the flexibility of active site regions, induced either by a temperature change or by the introduction of mutations, to experimentally observed losses of the enzyme function. As for applications, the results demonstrate that exploiting the principle of corresponding states not only allows for successful thermostability optimization but also for guiding experiments in order to improve enzyme activity in protein engineering. Proteins 2011. © 2010 Wiley-Liss, Inc.