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Multi-Scale Approaches in Drug Discovery

Multi-Scale Approaches in Drug Discovery
From Empirical Knowledge to In silico Experiments and Back

by Alejandro Speck-Planche

  • Publisher : Elsevier
  • Release : 2017-02-14
  • Pages : 238
  • ISBN : 008101242X
  • Language : En, Es, Fr & De
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Drug discovery is an expensive, time-consuming process and the modern drug discovery community is constantly challenged not only with discovering novel bioactive agents to combat resistance from known diseases and fight against new ones, but to do so in a way that is economically effective. Advances in both experimental and theoretical/computational methods envisage that the greatest challenges in drug discovery can be most successfully addressed by using a multi-scale approach, drawing on the specialties of a whole host of different disciplines. Multi-Scale Approaches to Drug Discovery furnishes chemists with the detail they need to identify drug leads with the highest potential before isolating and synthesizing them to produce effective drugs with greater swiftness than classical methods may allow. This significantly speeds up the search for more efficient therapeutic agents. After an introduction to multi-scale approaches outlining the need for and benefits of their use, the book goes on to explore a range of useful techniques and research areas, and their potential applications to this process. Profiling drug binding by thermodynamics, machine learning for predicting enzyme sub-classes, and multitasking models for computer-aided design and virtual compound screening are discussed, before the book goes on to review Alkaloid Menispermaceae leads, natural chemotherapeutic agents and methods for speeding up the design and virtual screening of therapeutic peptides. Flavonoids as multi-target compounds are then explored, before the book concludes with a review of Quasi-SMILES as a novel tool. Collecting together reviews and original research contributions written by leading experts in the field, Multi-Scale Approaches to Drug Discovery highlights cutting-edge approaches and practical examples of their implementation for those involved in the drug discovery process at many different levels. Using the combined knowledge of medicinal, computational, pharmaceutical and bio- chemists, it aims to support growth in the multi-scale approach to promote greater success in the development of new drugs. Offers practical guidance on ways to implement multiscale approaches for increased efficiency in drug discovery Draws on the experience of a highly skilled team of authors under the editorial guidance of one of the field's leading experts Includes cutting-edge techniques at the forefront of medicinal chemistry and drug discovery optimization

Programs and Services

Programs and Services
A Book

by National Library of Medicine (U.S.)

  • Publisher : Unknown Publisher
  • Release : 2006
  • Pages : 329
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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National Library of Medicine Programs and Services

National Library of Medicine Programs and Services
A Book

by National Library of Medicine (U.S.)

  • Publisher : Unknown Publisher
  • Release : 2007
  • Pages : 329
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Multiscale Approaches to Protein Modeling

Multiscale Approaches to Protein Modeling
A Book

by Andrzej Kolinski

  • Publisher : Springer Science & Business Media
  • Release : 2010-10-13
  • Pages : 355
  • ISBN : 9781441968890
  • Language : En, Es, Fr & De
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The book gives a comprehensive review of the most advanced multiscale methods for protein structure prediction, computational studies of protein dynamics, folding mechanisms and macromolecular interactions. It approaches span a wide range of the levels of coarse-grained representations, various sampling techniques and variety of applications to biomedical and biophysical problems. This book is intended to be used as a reference book for those who are just beginning their adventure with biomacromolecular modeling but also as a valuable source of detailed information for those who are already experts in the field of biomacromolecular modeling and in related areas of computational biology or biophysics.

Multiscale Computational Methods in Chemistry and Physics

Multiscale Computational Methods in Chemistry and Physics
A Book

by Achi Brandt,Jerzy Bernholc,Kurt Binder,K. Binder

  • Publisher : Ios PressInc
  • Release : 2001
  • Pages : 363
  • ISBN : 9781586031411
  • Language : En, Es, Fr & De
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This book brings together interdisciplinary contributions ranging from applied mathematics, theoretical physics, quantum chemistry and molecular biology, all addressing various facets of the problem to connect the many different scales that one has to deal with in the computer simulation of many systems of interest in chemistry (e.g. polymeric materials, biological molecules, clusters, surface and interface structure). Particular emphasis is on the -multigrid technique - and its applications, ranging from electronic structure calculations to the statistical mechanics of polymers.

Phenotypic screening in the 21st century

Phenotypic screening in the 21st century

by Gul Erdemli,Birgit T Priest

  • Publisher : Frontiers Media SA
  • Release : 2015-04-21
  • Pages : 329
  • ISBN : 2889194698
  • Language : En, Es, Fr & De
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In the genomic era of 1990s-2000s, pharmaceutical research moved to target-based drug discovery which enabled development of a number of small molecule drugs against a wide range of diseases. In many cases however, drugs that arose from genomics failed, questioning the validity of the targets and the suitability of target-based drug discovery as an optimal strategy for all disease states. For monogenic diseases, target-based approaches may be well-suited to the identification of novel therapies. Most diseases, however, are caused by a combination of several genetic and environmental factors and are likely to require simultaneous modulation of multiple molecular targets/pathways for successful treatment. For such diseases, reductionist approaches focusing on individual targets rather than biological networks are unlikely to succeed and new drug development strategies are required. In search of more successful approaches, the pharmaceutical industry is moving towards phenotypic screening beyond individual genes/targets. However, this requires rethinking of diseases and drug discovery approaches from a network and systems biology perspective. Since returning to the pre-genomics era of screening drug candidates in laborious animal models is not a feasible solution, the industry needs to evolve a new paradigm of phenotypic drug discovery within the context of systems biology. Such a paradigm must combine physiologically and disease relevant biological substrates with sufficient throughput, operational simplicity and statistical vigour. Biomarker strategies for translational medicine, as well as preclinical safety and selectivity assessments, would also need to be revised to adapt to the target agnostic style. This focused issue aims to discuss strategies, key concepts and technologies related to systems-based approaches in drug development. Design and implementation of innovative biological assays, featuring multiple target strategies, and rational drug design in the absence of target knowledge during the early drug discovery are illustrated with examples. Specific topics include: • The need for systems-based approaches in drug development • Phenotypic screening strategies • Compound libraries (natural product inspired compound collections) • Target deconvolution and identification • Target agnostic lead discovery and optimization • Multi-target approaches and decoding the phenotype (understanding biological interactions and multiscale systems modelling) • Translational aspects • Early evaluation of selectivity and safety in a target agnostic manner

Multiscale Cancer Modeling

Multiscale Cancer Modeling
A Book

by Thomas S. Deisboeck,Georgios S. Stamatakos

  • Publisher : CRC Press
  • Release : 2010-12-08
  • Pages : 484
  • ISBN : 9781439814420
  • Language : En, Es, Fr & De
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Cancer is a complex disease process that spans multiple scales in space and time. Driven by cutting-edge mathematical and computational techniques, in silico biology provides powerful tools to investigate the mechanistic relationships of genes, cells, and tissues. It enables the creation of experimentally testable hypotheses, the integration of data across scales, and the prediction of tumor progression and treatment outcome (in silico oncology). Drawing on an interdisciplinary group of distinguished international experts, Multiscale Cancer Modeling discusses the scientific and technical expertise necessary to conduct innovative cancer modeling research across scales. It presents contributions from some of the top in silico modeling groups in the United States and Europe. The ultimate goal of multiscale modeling and simulation approaches is their use in clinical practice, such as supporting patient-specific treatment optimization. This volume covers state-of-the-art methods of multiscale cancer modeling and addresses the field’s potential as well as future challenges. It encourages collaborations among researchers in various disciplines to achieve breakthroughs in cancer modeling.

Multiscale Modeling for Process Safety Applications

Multiscale Modeling for Process Safety Applications
A Book

by Arnab Chakrabarty,Sam Mannan,Tahir Cagin

  • Publisher : Butterworth-Heinemann
  • Release : 2015-11-29
  • Pages : 444
  • ISBN : 0123972833
  • Language : En, Es, Fr & De
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Multiscale Modeling for Process Safety Applications is a new reference demonstrating the implementation of multiscale modeling techniques on process safety applications. It is a valuable resource for readers interested in theoretical simulations and/or computer simulations of hazardous scenarios. As multi-scale modeling is a computational technique for solving problems involving multiple scales, such as how a flammable vapor cloud might behave if ignited, this book provides information on the fundamental topics of toxic, fire, and air explosion modeling, as well as modeling jet and pool fires using computational fluid dynamics. The book goes on to cover nanomaterial toxicity, QPSR analysis on relation of chemical structure to flash point, molecular structure and burning velocity, first principle studies of reactive chemicals, water and air reactive chemicals, and dust explosions. Chemical and process safety professionals, as well as faculty and graduate researchers, will benefit from the detailed coverage provided in this book. Provides the only comprehensive source addressing the use of multiscale modeling in the context of process safety Bridges multiscale modeling with process safety, enabling the reader to understand mapping between problem detail and effective usage of resources Presents an overall picture of addressing safety problems in all levels of modeling and the latest approaches to each in the field Features worked out examples, case studies, and a question bank to aid understanding and involvement for the reader

Bioinformatics and Computational Biology in Drug Discovery and Development

Bioinformatics and Computational Biology in Drug Discovery and Development
A Book

by William T. Loging

  • Publisher : Cambridge University Press
  • Release : 2016-02-29
  • Pages : 248
  • ISBN : 0521768004
  • Language : En, Es, Fr & De
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A comprehensive overview of the use of computational biology approaches in the drug discovery and development process.

Journal of the Royal Society, Interface

Journal of the Royal Society, Interface
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2005
  • Pages : 329
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Multiscale Operational Organic Chemistry

Multiscale Operational Organic Chemistry
A Problem-solving Approach to the Laboratory Course

by John W. Lehman

  • Publisher : Pearson College Division
  • Release : 2002
  • Pages : 854
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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This practical laboratory book provides both microscale and multiscale experiments. It encourages readers to think in the laboratory by solving a scientific problem in the process of carrying out an experiment. An “operational” approach is featured, equipping readers to master the major lab operations as they carry out problem solving experiments. Over 400 problems and exercises are provided. A valuable reference for organic chemists and chemical technicians.

Dissertation Abstracts International

Dissertation Abstracts International
The sciences and engineering. B

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2008
  • Pages : 329
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Semantic Breakthrough in Drug Discovery

Semantic Breakthrough in Drug Discovery
A Book

by Bin Chen,Huijun Wang,Ying Ding,David Wild

  • Publisher : Morgan & Claypool Publishers
  • Release : 2014-10-01
  • Pages : 142
  • ISBN : 1627054510
  • Language : En, Es, Fr & De
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The current drug development paradigm---sometimes expressed as, ``One disease, one target, one drug''---is under question, as relatively few drugs have reached the market in the last two decades. Meanwhile, the research focus of drug discovery is being placed on the study of drug action on biological systems as a whole, rather than on individual components of such systems. The vast amount of biological information about genes and proteins and their modulation by small molecules is pushing drug discovery to its next critical steps, involving the integration of chemical knowledge with these biological databases. Systematic integration of these heterogeneous datasets and the provision of algorithms to mine the integrated datasets would enable investigation of the complex mechanisms of drug action; however, traditional approaches face challenges in the representation and integration of multi-scale datasets, and in the discovery of underlying knowledge in the integrated datasets. The Semantic Web, envisioned to enable machines to understand and respond to complex human requests and to retrieve relevant, yet distributed, data, has the potential to trigger system-level chemical-biological innovations. Chem2Bio2RDF is presented as an example of utilizing Semantic Web technologies to enable intelligent analyses for drug discovery. Table of Contents: Introduction / Data Representation and Integration Using RDF / Data Representation and Integration Using OWL / Finding Complex Biological Relationships in PubMed Articles using Bio-LDA / Integrated Semantic Approach for Systems Chemical Biology Knowledge Discovery / Semantic Link Association Prediction / Conclusions / References / Authors' Biographies

Chemical Engineering Progress

Chemical Engineering Progress
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2009
  • Pages : 329
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Drug Delivery Systems: Advanced Technologies Potentially Applicable in Personalised Treatment

Drug Delivery Systems: Advanced Technologies Potentially Applicable in Personalised Treatment
A Book

by Jorge Coelho

  • Publisher : Springer Science & Business Media
  • Release : 2013-03-15
  • Pages : 421
  • ISBN : 9400760108
  • Language : En, Es, Fr & De
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This book is part of a series dedicated to recent advances on preventive, predictive and personalised medicine (PPPM). It focuses on the theme of “Drug delivery systems: advanced technologies potentially applicable in personalised treatments”. The critical topics involving the development and preparation of effective drug delivery systems, such as: polymers available, self-assembly, nanotechnology, pharmaceutical formulations, three dimensional structures, molecular modeling, tailor-made solutions and technological tendencies, are carefully discussed. The understanding of these areas constitutes a paramount route to establish personalised and effective solutions for specific diseases and individuals.

Drug Design Strategies

Drug Design Strategies
Computational Techniques and Applications

by Lee Banting,Tim Clark

  • Publisher : Royal Society of Chemistry
  • Release : 2012-01-04
  • Pages : 464
  • ISBN : 1849733406
  • Language : En, Es, Fr & De
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This book documents the latest research into the theory and application of force-fields, semi-empirical molecular orbital, density functional and ab initio calculations, Quantum Mechanical (QM) based modelling, Atoms in Molecules (AIM) approach, and biomolecular dynamics. It also covers theory and application of 2D cheminformatics, QSAR/QSPR, ADME properties of drugs, drug docking/scoring protocols and approaches, topological methodology, and modelling accurate inhibition constants of enzymes. Finally, the book gives the theory and applications of multiscale modelling of proteins and biomolecular systems. The information need for a book in this area is due to the continuing rapid advance of firstly theoretical approaches, secondly software/hardware and lastly the successful application of the technology and this book fills a gap in the literature. The co-editors have extensive experience of teaching and researching in the field and the book includes contributions from cutting-edge academic and industrial researchers in their respective fields. It is essential reading for medicinal chemists, computational chemists and those in the pharmaceutical industry.

Science & Technology in Japan

Science & Technology in Japan
A Book

by Anonim

  • Publisher : Unknown Publisher
  • Release : 2006
  • Pages : 329
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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Drug Design Strategies

Drug Design Strategies
Quantitative Approaches

by David J. Livingstone,Andrew M. Davis

  • Publisher : Royal Society of Chemistry
  • Release : 2011-11
  • Pages : 498
  • ISBN : 1849731667
  • Language : En, Es, Fr & De
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Shows how different parts of the drug discovery process have developed, with particular emphasis on quantitative aspects and possible future progress.

Multiscale Simulation Approaches for Predicting Protein-Ligand Binding Kinetics

Multiscale Simulation Approaches for Predicting Protein-Ligand Binding Kinetics
A Book

by Benjamin Robert Jagger

  • Publisher : Unknown Publisher
  • Release : 2020
  • Pages : 129
  • ISBN : 9876543210XXX
  • Language : En, Es, Fr & De
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A detailed understanding of the interaction between a drug candidate molecule and its target is essential for the development, optimization, and efficacy prediction of a drug. Kinetic parameters such as the association rate and residence time of a molecule have been shown to better correlate with in vivo efficacy than more commonly used thermodynamic parameters. Efficient and accurate computational predictions of these quantities are therefore of great interest for their potential to inform and improve the development of novel pharmaceuticals. In this dissertation, I present the development and application of a multiscale molecular simulation approach which combines molecular dynamics and Brownian dynamics simulations with the theory of milestoning to efficiently calculate protein-ligand binding and unbinding rates. I begin with an overview of many of the existing multiscale simulation approaches for studying drug-protein binding. Then I present the methodology we have developed, Simulation Enabled Estimation of Kinetic Rates (SEEKR), and demonstrate its effectiveness for predicting the association and dissociation rates of the inhibitor, benzamidine, to the trypsin protein; a common model system. I then present the effectiveness of our multiscale milestoning approach for rank-ordering a series of chemically diverse ligands to the model system [beta]-cyclodextrin. This study includes a direct comparison of both efficiency and accuracy to long timescale molecular dynamics simulations and also outlines best practices for the use of our approach and the assessment of sampling convergence. Finally, I present the implementation of a new milestoning algorithm, Markovian Milestoning with Voronoi Tesselations, in our multiscale methodology to significantly decrease the simulation cost of kinetics calculations, improve the assessment of sampling convergence, and provide a framework for the future development of additional capabilities with the SEEKR method. This study also includes the development and deployment of our toolkit along with documentation and tutorials to facilitate its use and continued improvement by the scientific community.

Systems Pharmacology and Pharmacodynamics

Systems Pharmacology and Pharmacodynamics
A Book

by Donald E. Mager,Holly H.C. Kimko

  • Publisher : Springer
  • Release : 2016-11-29
  • Pages : 511
  • ISBN : 3319445340
  • Language : En, Es, Fr & De
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While systems biology and pharmacodynamics have evolved in parallel, there are significant interrelationships that can enhance drug discovery and enable optimized therapy for each patient. Systems pharmacology is the relatively new discipline that is the interface between these two methods. This book is the first to cover the expertise from systems biology and pharmacodynamics researchers, describing how systems pharmacology may be developed and refined further to show practical applications in drug development. There is a growing awareness that pharmaceutical companies should reduce the high attrition in the pipeline due to insufficient efficacy or toxicity found in proof-of-concept and/or Phase II studies. Systems Pharmacology and Pharmacodynamics discusses the framework for integrating information obtained from understanding physiological/pathological pathways (normal body function system vs. perturbed system due to disease) and pharmacological targets in order to predict clinical efficacy and adverse events through iterations between mathematical modeling and experimentation.