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Articles 1 - 9 of 9
Full-Text Articles in Physical Sciences and Mathematics
The Mycobacterium Tuberculosis Drugome And Its Polypharmacological Implications, Sarah L. Kinnings, Li Xie, Kingston H. Fung, Richard M. Jackson, Lei Xie, Phillip E. Bourne
The Mycobacterium Tuberculosis Drugome And Its Polypharmacological Implications, Sarah L. Kinnings, Li Xie, Kingston H. Fung, Richard M. Jackson, Lei Xie, Phillip E. Bourne
Publications and Research
We report a computational approach that integrates structural bioinformatics, molecular modelling and systems biology to construct a drug-target network on a structural proteome-wide scale. The approach has been applied to the genome of Mycobacterium tuberculosis (M.tb), the causative agent of one of today’s most widely spread infectious diseases. The resulting drug-target interaction network for all structurally characterized approved drugs bound to putative M.tb receptors, we refer to as the ‘TB-drugome’. The TB-drugome reveals that approximately one-third of the drugs examined have the potential to be repositioned to treat tuberculosis and that many currently unexploited M.tb receptors may be chemically druggable …
Drug Off-Target Effects Predicted Using Structural Analysis In The Context Of A Metabolic Network Model, Roger L. Chang, Lei Xie, Philip E. Bourne, Bernhard O. Palsson
Drug Off-Target Effects Predicted Using Structural Analysis In The Context Of A Metabolic Network Model, Roger L. Chang, Lei Xie, Philip E. Bourne, Bernhard O. Palsson
Publications and Research
Recent advances in structural bioinformatics have enabled the prediction of protein-drug off-targets based on their ligand binding sites. Concurrent developments in systems biology allow for prediction of the functional effects of system perturbations using large-scale network models. Integration of these two capabilities provides a framework for evaluating metabolic drug response phenotypes in silico. This combined approach was applied to investigate the hypertensive side effect of the cholesteryl ester transfer protein inhibitor torcetrapib in the context of human renal function. A metabolic kidney model was generated in which to simulate drug treatment. Causal drug off-targets were predicted that have previously been …
Enumeration Refactoring: A Tool For Automatically Converting Java Constants To Enumerated Types, Raffi T. Khatchadourian, Benjamin Muskalla
Enumeration Refactoring: A Tool For Automatically Converting Java Constants To Enumerated Types, Raffi T. Khatchadourian, Benjamin Muskalla
Publications and Research
Java 5 introduces several new features that significantly improve older Java technology. We consider the new enum construct, which provides language support for enumerated types. Before Java 5, programmers needed to employ various patterns to compensate for the absence of enumerated types in Java. Unfortunately, these compensation patterns lack several highly desirable properties of the enum construct, notably type-safety. We demonstrate an automated refactoring tool called Convert Constants to Enum for transforming legacy Java code to use the new enumeration construct. An interprocedural type inferencing algorithm that tracks the flow of enumerated values drives the approach, and the tool is …
Smap-Ws: A Parallel Web Service For Structural Proteome-Wide Ligand-Binding Site Comparison, Jingyuan Ren, Lei Xie, Wilfred W. Li, Philip E. Bourne
Smap-Ws: A Parallel Web Service For Structural Proteome-Wide Ligand-Binding Site Comparison, Jingyuan Ren, Lei Xie, Wilfred W. Li, Philip E. Bourne
Publications and Research
The proteome-wide characterization and analysis of protein ligand-binding sites and their interactions with ligands can provide pivotal information in understanding the structure, function and evolution of proteins and for designing safe and efficient therapeutics. The SMAP web service (SMAP-WS) meets this need through parallel computations designed for 3D ligand-binding site comparison and similarity searching on a structural proteome scale. SMAP-WS implements a shape descriptor (the Geometric Potential) that characterizes both local and global topological properties of the protein structure and which can be used to predict the likely ligand-binding pocket [Xie,L. and Bourne,P.E. (2007) A robust and efficient algorithm for …
Tredd—A Database For Tandem Repeats Over The Edit Distance, Dina Sokol, Firat Atagun
Tredd—A Database For Tandem Repeats Over The Edit Distance, Dina Sokol, Firat Atagun
Publications and Research
A ‘tandem repeat’ in DNA is a sequence of two or more contiguous, approximate copies of a pattern of nucleotides. Tandem repeats are common in the genomes of both eukaryotic and prokaryotic organisms. They are significant markers for human identity testing, disease diagnosis, sequence homology and population studies. In this article, we describe a new database, TRedD, which contains the tandem repeats found in the human genome. The database is publicly available online, and the software for locating the repeats is also freely available. The definition of tandem repeats used by TRedD is a new and innovative definition based upon …
What The 2007 Tac Market Design Game Tells Us About Effective Auction Mechanisms, Jinzhong Niu, Kai Cai, Simon Parsons, Peter Mcburney, Enrico Gerding
What The 2007 Tac Market Design Game Tells Us About Effective Auction Mechanisms, Jinzhong Niu, Kai Cai, Simon Parsons, Peter Mcburney, Enrico Gerding
Publications and Research
This paper analyzes the entrants to the 2007 TAC Market Design Game. We present a classification of the entries to the competition, and use this classification to compare these entries. The paper also attempts to relate market dynamics to the auction rules adopted by these entries and their adaptive strategies via a set of post-tournament experiments. Based on this analysis, the paper speculates about the design of effective auction mechanisms, both in the setting of this competition and in the more general case.
A Multidimensional Strategy To Detect Polypharmacological Targets In The Absence Of Structural And Sequence Homology, Jacob D. Durrant, Rommie E. Amaro, Lei Xie, Michael D. Urbaniak, Michael A. J. Ferguson, Antti Haapalainen, Zhijun Chen, Anne Marie Di Guilmi, Frank Wunder, Philip E. Bourne, J. Andrew Mccammon
A Multidimensional Strategy To Detect Polypharmacological Targets In The Absence Of Structural And Sequence Homology, Jacob D. Durrant, Rommie E. Amaro, Lei Xie, Michael D. Urbaniak, Michael A. J. Ferguson, Antti Haapalainen, Zhijun Chen, Anne Marie Di Guilmi, Frank Wunder, Philip E. Bourne, J. Andrew Mccammon
Publications and Research
Conventional drug design embraces the ‘‘one gene, one drug, one disease’’ philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional …
Nearest Neighbor Search With Strong Location Privacy, Stavros Papadopoulos, Spiridon Bakiras, Dimitris Papadias
Nearest Neighbor Search With Strong Location Privacy, Stavros Papadopoulos, Spiridon Bakiras, Dimitris Papadias
Publications and Research
The tremendous growth of the Internet has significantly reduced the cost of obtaining and sharing information about individuals, raising many concerns about user privacy. Spatial queries pose an additional threat to privacy because the location of a query may be sufficient to reveal sensitive information about the querier. In this paper we focus on k nearest neighbor (kNN) queries and define the notion of strong location privacy, which renders a query indistinguishable from any location in the data space. We argue that previous work fails to support this property for arbitrary kNN search. Towards this end, we introduce methods that …
Arabic For Designers By Mourad Boutros, Saad D. Abulhab
Arabic For Designers By Mourad Boutros, Saad D. Abulhab
Publications and Research
No abstract provided.