Springer protocols feed by Pharmacology/Toxicology 
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This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.An In Silico Model for Interpreting Polypharmacology in Drug–Target Networks
This article introduces an efficient in silico method for enumerating, from given drug–target pairs, all frequent subgraph–subsequence pairs, which can then be further examined by hypothesis testing for statistical significance. Unique features of the method are its scalability, computational efficiency, and technical soundness in terms of computer science and statistics. The presented method was applied to 11,219 drug–target pairs in DrugBank to obtain significant substructure pairs, which can divide most of the original 11,219 pairs into eight highly exclusive clusters, implying that the obtained substr...
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
In Silico Models for Drug Resistance
We present two in silico models for the discovery of drug resistance mechanisms and for combating the evolution of resistance, respectively. In the first model, we computationally investigated subgraphs of a biological interaction network that show substantial adaptations when cells transcriptionally respond to a changing environment or treatment. As a case study, we investigated the response of the malaria parasite Plasmodium falciparum to chloroquine and tetracycline treatments. The second model involves a machine learning technique that combines clustering, common distance similarity measurements, and hierarchical clust...
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
Genome Comparisons as a Tool for Antimicrobial Target Discovery
Essential genes are frequently conserved among bacterial species and thus microbial and eukaryote genome comparisons can be used to compile datasets of homologous proteins and families that can be utilized to identify attractive targets for the design of antimicrobial agents and other drugs. These searches can now often be conducted using Web tools. A number of such resources that provide sequence information and comparative software as well as computational tools for convenient analysis of the data are summarized here and their step-by-step use explained. (Source: Springer protocols feed by Pharmacology/Toxicology)
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
In Silico Systems Biology Approaches for the Identification of Antimicrobial Targets
Classical antibiotic discovery efforts have relied mainly on molecular library screening coupled with target-based lead optimization. The conventional approaches are unable to tackle the emergence of antibiotic resistance and are failing to provide understanding of multiple mechanisms behind drug actions and the off-target effects. These insufficiencies have prompted researchers to focus on a multidisciplinary approach of systems biology-based antibiotic discovery. Systems biology is capable of providing a big-picture view for therapeutic targets through interconnected networks of biochemical reactions derived from both ex...
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
Virtual Screening in Drug Design
Virtual screening has become a standard tool in drug discovery to identify novel lead compounds that target a biomolecule of interest. I present several concepts in ligand-based and structure-based virtual screening and discuss some of the current shortcomings and new developments. I also highlight approaches that combine concepts from structure- and ligand-based design. (Source: Springer protocols feed by Pharmacology/Toxicology)
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
Computational Models for Tuberculosis Drug Discovery
The search for small molecules with activity against Mycobacterium tuberculosis increasingly uses high-throughput screening and computational methods. Previously, we have analyzed recent studies in which computational tools were used for cheminformatics. We have now updated this analysis to illustrate how they may assist in finding desirable leads for tuberculosis drug discovery. We provide our thoughts on strategies for drug discovery efforts for neglected diseases. (Source: Springer protocols feed by Pharmacology/Toxicology)
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
Designing Novel Inhibitors of Trypanosoma brucei
Computational simulations of essential biological systems in pathogenic organisms are increasingly being used to reveal structural and dynamical features for targets of interest. At the same time, increased research efforts, especially from academia, have been directed toward drug discovery for neglected tropical diseases. Although these diseases cripple large populations in less fortunate parts of the world, either very few new drugs are being developed or the available treatments for them have severe side effects, including death. This chapter walks readers through a computational investigation used to find novel inhibit...
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
Malarial Kinases: Novel Targets for In Silico Approaches to Drug Discovery
Malaria, the disease caused by infection with protozoan parasites from the genus Plasmodium, claims the lives of nearly 1 million people annually. Developing nations, particularly in the African Region, bear the brunt of this malaria burden. Alarmingly, the most dangerous etiologic agent of malaria, Plasmodium falciparum, is becoming increasingly resistant to current first-line antimalarials. In light of the widespread devastation caused by malaria, the emergence of drug-resistant P. falciparum strains, and the projected decrease in funding for malaria eradication that may occur over the next decade, the identification of ...
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
Rational Design of HIV-1 Entry Inhibitors
This chapter reviews studies that have used in silico techniques to design or identify potential HIV-1 entry inhibitors targeting cellular receptors CD4, CCR5, and CXCR4 and envelope glycoproteins, gp120 and gp41 of HIV-1. Both structure- and ligand-based design techniques have been used in those studies by applying diverse modeling techniques such as quantitative structure–activity relationship analysis, conformational analysis, molecular dynamics, pharmacophore generation, docking, virtual screening (using docking software and also shape-based ROCS techniques), and fragment-based design. (Source: Springer protocols...
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
Identification of Novel Anthrax Toxin Countermeasures Using In Silico Methods
We present a selection of in silico virtual screening protocols incorporating docking and scoring, shape-based searching, and pharmacophore mapping techniques to identify and prioritize small molecules with potential biological activity against LF. We also recommend screening parameters that have been shown to increase the accuracy and reliability of these computational results. (Source: Springer protocols feed by Pharmacology/Toxicology)
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
Recognition of Nontrivial Remote Homology Relationships Involving Proteins of Helicobacter pylori: Implications for Function Recognition
This chapter explains techniques for recognition of nontrivial remote homology relationships involving proteins of Helicobacter pylori and their implications for function recognition. Using the remote homology detection method, employing multiple-profile representations for every protein domain family, remotely related domain family information has been assigned for the 122, 77, and 95 protein sequences of 26695, and J99, and HPAG1 strains of H. pylori, respectively. Relationships for some of the H. pylori protein sequences with Pfam domain families are reported for the first time. In publicly available domain databases su...
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
The Collaborative Drug Discovery (CDD) Database
The broad goals of Collaborative Drug Discovery (CDD) are to enable a collaborative “cloud-based” tool to be used to bring together neglected disease researchers and other researchers from usually separate areas, to collaborate and to share compounds and drug discovery data in the research community, which will ultimately result in long-term improvements in the research enterprise and health care delivery. This chapter briefly introduces CDD software and describes applications in antimalarial and tuberculosis research. (Source: Springer protocols feed by Pharmacology/Toxicology)
Source: Springer protocols feed by Pharmacology/Toxicology - April 13, 2013 Category: Drugs & Pharmacology Source Type: news
Combined MicroRNA In Situ Hybridization and Immunohistochemical Detection of Protein Markers
MicroRNAs are short (18-23 nucleotides) non-coding RNAs involved in posttranscriptional regulation of gene expression through their specific binding to the 3’UTR of mRNAs. MicroRNAs can be detected in tissues using specific locked nucleic acid (LNA)-enhanced probes. The characterization of microRNA expression in tissues by in situ detection is often crucial following a microRNA biomarker discovery phase in order to validate the candidate microRNA biomarker and allow better interpretation of its molecular functions and derived cellular interactions. The in situ hybridization data provides information about contextual ...
Source: Springer protocols feed by Pharmacology/Toxicology - February 26, 2013 Category: Drugs & Pharmacology Source Type: news
Bright-Field In Situ Hybridization Methods to Discover Gene Amplifications and Rearrangements in Clinical Samples
Brightfield in situ hybridization (BISH) applications have significant advantages over traditional fluorescence in situ hybridization (FISH). BISH slides can be analyzed using a regular microscope while FISH slides require the use of a specialized fluorescence microscope. BISH slides allow observers for correlating the gene status (gene amplifications, gene rearrangements, and gene deletions) and tissue morphology better than FISH slides. Also, BISH slides are ideal for the permanent preservation of gene signals. Furthermore, BISH applications can be optimized using an automated tissue slide processing system. BISH applica...
Source: Springer protocols feed by Pharmacology/Toxicology - February 26, 2013 Category: Drugs & Pharmacology Source Type: news
In Vivo Target Validation by Inducible RNAi in Human Xenograft Mouse Models
Proper target selection and validation are crucial to the discovery of new anti-cancer agents. Since tumors depend on a suitable microenvironment for their growth, once a putative target has been identified, its validation should be performed whenever possible in vivo. This chapter deals with the generation of human xenograft mouse models genetically modified to induce the modulation of cancer-related genes as an approach to validate oncology targets. (Source: Springer protocols feed by Pharmacology/Toxicology)
Source: Springer protocols feed by Pharmacology/Toxicology - February 26, 2013 Category: Drugs & Pharmacology Source Type: news
