Computational Biology In Drug Discovery And Repurposing

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Computational Biology in Drug Discovery and Repurposing

Author : Rajani Sharma
Publisher : CRC Press
ISBN 13 : 1000988708
Total Pages : 478 pages
Book Rating : 4.0/5 (9 download)

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Book Synopsis Computational Biology in Drug Discovery and Repurposing by : Rajani Sharma

Download or read book Computational Biology in Drug Discovery and Repurposing written by Rajani Sharma and published by CRC Press. This book was released on 2024-08-16 with total page 478 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new book takes an in-depth look at the emerging and prospective field of computational biology and bioinformatics, which possesses the ability to analyze large accumulated biological data collected from sequence analysis of proteins and genes and cell population with an aim to make new predictions pertaining to drug discovery and new biology. The book explains the basic methodology associated with a bioinformatics and computational approach in drug designing. It then goes on to cover the implementation of computational programming, bioinformatics, pharmacophore modeling, biotechnological techniques, and pharmaceutical chemistry in designing drugs. The major advantage of intervention of computer language or programming is to cut down the number of steps and costs in the field of drug designing, reducing the repeating steps and saving time in screening the potent component for drug or vaccine designing. The book describes algorithms used for drug designing and the use of machine learning and AI in drug delivery and disease diagnosis, which are valuable in clinical decision-making. The implementation of robotics in different diseases like stroke, cancer, COVID-19, etc. is also addressed. Topics include machine learning, AI, databases in drug design, molecular docking, bioinformatics tools, target-based drug design, and immunoinformatics, chemoinformatics, and nanoinformatics in drug design. Drug repurposing in drug design in general as well as for specific diseases, including cancer, Alzheimer’s disease, tuberculosis, COVID-19, etc., is also addressed in depth.

Computational Methods for Drug Repurposing

Author : Quentin Vanhaelen
Publisher : Humana
ISBN 13 : 9781493989546
Total Pages : 0 pages
Book Rating : 4.9/5 (895 download)

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Book Synopsis Computational Methods for Drug Repurposing by : Quentin Vanhaelen

Download or read book Computational Methods for Drug Repurposing written by Quentin Vanhaelen and published by Humana. This book was released on 2018-12-14 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed book explores techniques commonly used for research into drug repurposing, a well-known strategy to find alternative indications for drugs which have already undergone toxicology and pharma-kinetic studies but have failed later stages during the development, via computational methods. Thereby, it addresses the intense challenges of identifying the appropriate type of algorithm and relevant technical information for computational repurposing. Written for the highly successful Methods in Molecular Biology series, the authors of each chapter use their experience in the field to describe the implementation and successful use of a specific repurposing method thus providing lab-ready instruction. Authoritative and practical, Computational Methods for Drug Repurposing serves as an ideal guide to researchers interested in this vital area of drug development.

New Approach for Drug Repurposing Part A

Author :
Publisher : Elsevier
ISBN 13 : 0443223386
Total Pages : 406 pages
Book Rating : 4.4/5 (432 download)

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Book Synopsis New Approach for Drug Repurposing Part A by :

Download or read book New Approach for Drug Repurposing Part A written by and published by Elsevier. This book was released on 2024-06 with total page 406 pages. Available in PDF, EPUB and Kindle. Book excerpt: New approach for drug repurposing represents drug discovery and development which is a tedious process that requires 10-15 years of time, investments up to $1-2 billion, and have high risk of failure to enter into market for clinical applications. As the drugs has to pass through number of developmental phase, the likelihood for a drug to be approved from phase I clinical trial to United States of Food and Drug Administration (USFDA) approval is less than 10%. More than 90% of drugs failed in due to toxicity, efficacy and clinical trials. Drug repurposing is one of the roadway to accelerating drug discovery and development for treating disease and thus to providing better quality of life. This volume covers an overview of drug repurposing, novel methods, mechanism of action, lab on chip for drug repurposing, computational biology, system biology, artificial intelligence and machine learning for drug repurposing, target identification, target mining, high throughput drug screening, clinical trial of repurposed drug, repurposed biologics, and regulatory consideration and intellectual property right of repurposed drug. This volume highlights a number of aspects of the drug repurposing that can help the basic understanding of students, researchers, clinicians, entrepreneurs, and stakeholders to perform their research with great interest.

Bioinformatics and Computational Biology in Drug Discovery and Development

Author : William T. Loging
Publisher : Cambridge University Press
ISBN 13 : 0521768004
Total Pages : 255 pages
Book Rating : 4.5/5 (217 download)

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Book Synopsis Bioinformatics and Computational Biology in Drug Discovery and Development by : William T. Loging

Download or read book Bioinformatics and Computational Biology in Drug Discovery and Development written by William T. Loging and published by Cambridge University Press. This book was released on 2016-03-17 with total page 255 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive overview of the use of computational biology approaches in the drug discovery and development process.

Computational Approaches: Drug Discovery and Design in Medicinal Chemistry and Bioinformatics

Author : Marco Tutone
Publisher :
ISBN 13 : 9783036527789
Total Pages : 387 pages
Book Rating : 4.5/5 (277 download)

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Book Synopsis Computational Approaches: Drug Discovery and Design in Medicinal Chemistry and Bioinformatics by : Marco Tutone

Download or read book Computational Approaches: Drug Discovery and Design in Medicinal Chemistry and Bioinformatics written by Marco Tutone and published by . This book was released on 2021 with total page 387 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a collection of original research articles in the field of computer-aided drug design. It reports the use of current and validated computational approaches applied to drug discovery as well as the development of new computational tools to identify new and more potent drugs.

Drug Repositioning

Author : Michael J. Barratt
Publisher : John Wiley & Sons
ISBN 13 : 0470878274
Total Pages : 499 pages
Book Rating : 4.4/5 (78 download)

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Book Synopsis Drug Repositioning by : Michael J. Barratt

Download or read book Drug Repositioning written by Michael J. Barratt and published by John Wiley & Sons. This book was released on 2012-05-29 with total page 499 pages. Available in PDF, EPUB and Kindle. Book excerpt: The how's and why's of successful drug repositioning Drug repositioning, also known as drug reprofiling or repurposing, has become an increasingly important part of the drug development process. This book examines the business, technical, scientific, and operational challenges and opportunities that drug repositioning offers. Readers will learn how to perform the latest experimental and computational methods that support drug repositioning, and detailed case studies throughout the book demonstrate how these methods fit within the context of a comprehensive drug repositioning strategy. Drug Repositioning is divided into three parts: Part 1, Drug Repositioning: Business Case, Strategies, and Operational Considerations, examines the medical and commercial drivers underpinning the quest to reposition existing drugs, guiding readers through the key strategic, technical, operational, and regulatory decisions needed for successful drug repositioning programs. Part 2, Application of Technology Platforms to Uncover New Indications and Repurpose Existing Drugs, sets forth computational-based strategies, tools, and databases that have been designed for repositioning studies, screening approaches, including combinations of existing drugs, and a look at the development of chemically modified analogs of approved agents. Part 3, Academic and Non-Profit Initiatives & the Role of Alliances in the Drug Repositioning Industry, explores current investigations for repositioning drugs to treat rare and neglected diseases, which are frequently overlooked by for-profit pharmaceutical companies due to their lack of commercial return. The book's appendix provides valuable resources for drug repositioning researchers, including information on drug repositioning and reformulation companies, databases, government resources and organizations, regulatory agencies, and drug repositioning initiatives from academia and non-profits. With this book as their guide, students and pharmaceutical researchers can learn how to use drug repositioning techniques to extend the lifespan and applications of existing drugs as well as maximize the return on investment in drug research and development.

Computational Methods in Drug Discovery and Repurposing for Cancer Therapy

Author : Ganji Purnachandra Nagaraju
Publisher : Elsevier
ISBN 13 : 0443152810
Total Pages : 460 pages
Book Rating : 4.4/5 (431 download)

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Book Synopsis Computational Methods in Drug Discovery and Repurposing for Cancer Therapy by : Ganji Purnachandra Nagaraju

Download or read book Computational Methods in Drug Discovery and Repurposing for Cancer Therapy written by Ganji Purnachandra Nagaraju and published by Elsevier. This book was released on 2023-03-22 with total page 460 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational Methods in Drug Discovery and Repurposing for Cancer Therapy provides knowledge about ongoing research as well as computational approaches for drug discovery and repurposing for cancer therapy. The book also provides detailed descriptions about target molecules, pathways, and their inhibitors for easy understanding and applicability. The book discusses tools and techniques such as integrated bioinformatics approaches, systems biology tools, molecular docking, computational chemistry, artificial intelligence, machine learning, structure-based virtual screening, biomarkers, and transcriptome; those are discussed in the context of different cancer types, such as colon, pancreatic, glioblastoma, endometrial, and retinoblastoma, among others. This book is a valuable resource for researchers, students, and members of the biomedical and medical fields who want to learn more about the use of computational modeling to better tailor the treatment for cancer patients. Discusses in silico remodeling of effective phytochemical compounds for discovering improved anticancer agents for substantial/significant cancer therapy Covers potential tools of bioinformatics that are applied toward discovering new targets by drug repurposing and strategies to cure different types of cancers Demonstrates the significance of computational and artificial intelligence approaches in anticancer drug discovery Explores how these various advances can be integrated into a precision and personalized medicine approach that can eventually enhance patient care

Drug Repurposing

Author : Farid A. Badria
Publisher : BoD – Books on Demand
ISBN 13 : 1839685204
Total Pages : 236 pages
Book Rating : 4.8/5 (396 download)

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Book Synopsis Drug Repurposing by : Farid A. Badria

Download or read book Drug Repurposing written by Farid A. Badria and published by BoD – Books on Demand. This book was released on 2020-12-02 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug repurposing or drug repositioning is a new approach to presenting new indications for common commercial and clinically approved existing drugs. For example, chloroquine, an old antimalarial drug, showed promising results for treating COVID-19, interfering with MDR in several types of cancer, and chemosensitizing human leukemic cells.This book focuses on the hypothesis, risk/benefits, and economic impacts of drug repurposing on drug discovery in dermatology, infectious diseases, neurological disorders, cancer, and orphan diseases. It brings together up-to-date research to provide readers with an informative, illustrative, and easy-to-read book useful for students, clinicians, and the pharmaceutical industry.

Current Trends in Computational Modeling for Drug Discovery

Author : Supratik Kar
Publisher : Springer Nature
ISBN 13 : 3031338715
Total Pages : 311 pages
Book Rating : 4.0/5 (313 download)

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Book Synopsis Current Trends in Computational Modeling for Drug Discovery by : Supratik Kar

Download or read book Current Trends in Computational Modeling for Drug Discovery written by Supratik Kar and published by Springer Nature. This book was released on 2023-06-30 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt: This contributed volume offers a comprehensive discussion on how to design and discover pharmaceuticals using computational modeling techniques. The different chapters deal with the classical and most advanced techniques, theories, protocols, databases, and tools employed in computer-aided drug design (CADD) covering diverse therapeutic classes. Multiple components of Structure-Based Drug Discovery (SBDD) along with its workflow and associated challenges are presented while potential leads for Alzheimer’s disease (AD), antiviral agents, anti-human immunodeficiency virus (HIV) drugs, and leads for Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) disease are discussed in detail. Computational toxicological aspects in drug design and discovery, screening adverse effects, and existing or future in silico tools are highlighted, while a novel in silico tool, RASAR, which can be a major technique for small to big datasets when not much experimental data are present, is presented. The book also introduces the reader to the major drug databases covering drug molecules, chemicals, therapeutic targets, metabolomics, and peptides, which are great resources for drug discovery employing drug repurposing, high throughput, and virtual screening. This volume is a great tool for graduates, researchers, academics, and industrial scientists working in the fields of cheminformatics, bioinformatics, computational biology, and chemistry.

Drug Repurposing and Computational Drug Discovery

Author : Mithun Rudrapal
Publisher : CRC Press
ISBN 13 : 1000800016
Total Pages : 294 pages
Book Rating : 4.0/5 (8 download)

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Book Synopsis Drug Repurposing and Computational Drug Discovery by : Mithun Rudrapal

Download or read book Drug Repurposing and Computational Drug Discovery written by Mithun Rudrapal and published by CRC Press. This book was released on 2023-10-27 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug repurposing is defined as identifying new pharmacological indications from old, existing, failed, investigational, already marketed, or FDA-approved drugs and prodrugs, and applying these new uses in the treatment of diseases other than the drug’s original intended therapeutic use. The application of computational techniques in discovery research not only helps in the development of drugs from leads or existing drug molecules but can also be useful for the repurposing of existing drug candidates. This new volume presents exciting recent advances in drug repurposing and computational approaches for the discovery and development of drugs against certain difficult-to-treat and life-threatening diseases. With contributions from a global team of experts (academicians, scientists, and researchers), it explores the sophisticated tools and techniques of drug repurposing and computational drug discovery. It delivers valuable information on computational techniques, tools, and databases being utilized for drug repurposing and for identifying the uses of existing drug candidates on different emerging or deadly diseases. Drug repurposing and computational approaches addressed in the book target the discovery and development of drugs for microbial infections (bacterial, fungal, viral, COVID-19), parasitic diseases and neglected tropical diseases (NTDs), malignant diseases (cancer), inflammatory diseases, cardiovascular disorders, diabetes, and aging and neurological (CNS) disorders. In addition, the challenges and regulatory issues encountered in drug repurposing and computational drug discovery programs are looked at, offering perspectives for future directions.

Drug Repurposing and Repositioning

Author : Institute of Medicine
Publisher : National Academies Press
ISBN 13 : 0309302072
Total Pages : 95 pages
Book Rating : 4.3/5 (93 download)

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Book Synopsis Drug Repurposing and Repositioning by : Institute of Medicine

Download or read book Drug Repurposing and Repositioning written by Institute of Medicine and published by National Academies Press. This book was released on 2014-08-08 with total page 95 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug development can be time-consuming and expensive. Recent estimates suggest that, on average, it takes 10 years and at least $1 billion to bring a drug to market. Given the time and expense of developing drugs de novo, pharmaceutical companies have become increasingly interested in finding new uses for existing drugs - a process referred to as drug repurposing or repositioning. Historically, drug repurposing has been largely an unintentional, serendipitous process that took place when a drug was found to have an offtarget effect or a previously unrecognized on-target effect that could be used for identifying a new indication. Perhaps the most recognizable example of such a successful repositioning effort is sildenafil. Originally developed as an anti-hypertensive, sildenafil, marketed as Viagra and under other trade names, has been repurposed for the treatment of erectile dysfunction and pulmonary arterial hypertension. Viagra generated more than $2 billion worldwide in 2012 and has recently been studied for the treatment of heart failure. Given the widespread interest in drug repurposing, the Roundtable on Translating Genomic-Based Research for Health of the Institute of Medicine hosted a workshop on June 24, 2013, in Washington, DC, to assess the current landscape of drug repurposing activities in industry, academia, and government. Stakeholders, including government officials, pharmaceutical company representatives, academic researchers, regulators, funders, and patients, were invited to present their perspectives and to participate in workshop discussions. Drug Repurposing and Repositioning is the summary of that workshop. This report examines enabling tools and technology for drug repurposing; evaluates the business models and economic incentives for pursuing a repurposing approach; and discusses how genomic and genetic research could be positioned to better enable a drug repurposing paradigm.

CADD and Informatics in Drug Discovery

Author : Mithun Rudrapal
Publisher : Springer Nature
ISBN 13 : 9819913160
Total Pages : 370 pages
Book Rating : 4.8/5 (199 download)

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Book Synopsis CADD and Informatics in Drug Discovery by : Mithun Rudrapal

Download or read book CADD and Informatics in Drug Discovery written by Mithun Rudrapal and published by Springer Nature. This book was released on 2023-05-12 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book updates knowledge on recent advances in computational, biophysical and bioinformatics tools/techniques and their practical applications in modern drug design and discovery paradigm. It also encompasses fundamental principles, advanced methodologies and applications of various CADD approaches including several cutting-edge areas; presenting recent developments covering ongoing trends in the field of computer-aided drug discovery. Having contributions by a global team of experts, the book is expected to be an ideal resource for drug discovery scientists, medicinal chemists, pharmacologists, toxicologists, phytochemists, biochemists, biologists, R&D personnel, researchers, students, teachers and those working in the field of drug discovery. It will fill the knowledge gaps that exist in the current CADD approaches and methodologies/ protocols being widely used in both academic and research practices. Further, a special focus on current status of various computational drug design approaches (SBDD, LBDD, de novo drug design, pharmacophore-based search), bioinformatics tools and databases, computational screening and modeling of phytochemicals/natural products, artificial intelligence and machine learning, and network pharmacology and systems biology would certainly guide researchers, students or readers to conduct their research in the emerging area(s) of interest. It is also expected to be highly beneficial to various stakeholders working in the pharmaceutical and biotechnology industries (R&D), the academic as well as research sectors.

Computational Drug Design

Author : D. C. Young
Publisher : John Wiley & Sons
ISBN 13 : 9780470451847
Total Pages : 344 pages
Book Rating : 4.4/5 (518 download)

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Book Synopsis Computational Drug Design by : D. C. Young

Download or read book Computational Drug Design written by D. C. Young and published by John Wiley & Sons. This book was released on 2009-01-28 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: Helps you choose the right computational tools and techniques to meet your drug design goals Computational Drug Design covers all of the major computational drug design techniques in use today, focusing on the process that pharmaceutical chemists employ to design a new drug molecule. The discussions of which computational tools to use and when and how to use them are all based on typical pharmaceutical industry drug design processes. Following an introduction, the book is divided into three parts: Part One, The Drug Design Process, sets forth a variety of design processes suitable for a number of different drug development scenarios and drug targets. The author demonstrates how computational techniques are typically used during the design process, helping readers choose the best computational tools to meet their goals. Part Two, Computational Tools and Techniques, offers a series of chapters, each one dedicated to a single computational technique. Readers discover the strengths and weaknesses of each technique. Moreover, the book tabulates comparative accuracy studies, giving readers an unbiased comparison of all the available techniques. Part Three, Related Topics, addresses new, emerging, and complementary technologies, including bioinformatics, simulations at the cellular and organ level, synthesis route prediction, proteomics, and prodrug approaches. The book's accompanying CD-ROM, a special feature, offers graphics of the molecular structures and dynamic reactions discussed in the book as well as demos from computational drug design software companies. Computational Drug Design is ideal for both students and professionals in drug design, helping them choose and take full advantage of the best computational tools available. Note: CD-ROM/DVD and other supplementary materials are not included as part of eBook file.

Statistics and Data Analysis for Microarrays Using R and Bioconductor

Author : Sorin Draghici
Publisher : CRC Press
ISBN 13 : 1439809763
Total Pages : 1036 pages
Book Rating : 4.4/5 (398 download)

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Book Synopsis Statistics and Data Analysis for Microarrays Using R and Bioconductor by : Sorin Draghici

Download or read book Statistics and Data Analysis for Microarrays Using R and Bioconductor written by Sorin Draghici and published by CRC Press. This book was released on 2016-04-19 with total page 1036 pages. Available in PDF, EPUB and Kindle. Book excerpt: Richly illustrated in color, Statistics and Data Analysis for Microarrays Using R and Bioconductor, Second Edition provides a clear and rigorous description of powerful analysis techniques and algorithms for mining and interpreting biological information. Omitting tedious details, heavy formalisms, and cryptic notations, the text takes a hands-on,

Drug Repurposing

Author : Mithun Rudrapal
Publisher : BoD – Books on Demand
ISBN 13 : 1837687765
Total Pages : 225 pages
Book Rating : 4.8/5 (376 download)

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Book Synopsis Drug Repurposing by : Mithun Rudrapal

Download or read book Drug Repurposing written by Mithun Rudrapal and published by BoD – Books on Demand. This book was released on 2023-06-07 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug repurposing (or drug repositioning) is defined as the process of identifying new pharmacological indications of old, existing, investigational, or FDA-approved drugs for use in the treatment of diseases other than the drugs’ original intended therapeutic use. Drug Repurposing - Advances, Scopes and Opportunities in Drug Discovery delivers up-to-date information on the identification of newer uses, molecular mechanisms, and novel targets of existing drug candidates through the application of various experimental, biophysical, and computational approaches and techniques. Chapters discuss recent advances in drug repurposing strategies that are currently being used in the discovery and development of drugs against difficult-to-treat, rare, and life-threatening diseases, including microbial infections, COVID-19, parasitic diseases, cardiovascular diseases, neurological disorders, and cancer. The book also discusses the modern experimental assays (HTS) and computational techniques including informatics and databases, molecular docking and dynamics, artificial intelligence and machine learning, virtual screening and pharmacophore modeling, proteomics and metabolomics, and network pharmacology and systems biology approaches. Some of the key features of the book are: • Presents the strategies available for the development of drugs by drug repurposing approaches through various experimental and computational techniques for the treatment of difficult-to-treat, rare, and deadly diseases • Summarizes the latest advances in the application of drug repurposing strategies, techniques, and approaches in the discovery and development of drugs • Depicts drug development approaches from existing drug candidates and/or lead molecules through modern experimental assays, biophysical tools, and computational techniques Written by a global team of experts, this book is useful for drug discovery scientists, drug developers, medicinal chemists, phytochemists, pharmacologists, clinicians, biochemists, biomedical scientists, healthcare professionals, researchers, teaching faculty, and students.

Systems Biology in Drug Discovery and Development

Author : Daniel L. Young
Publisher : John Wiley & Sons
ISBN 13 : 1118016424
Total Pages : 398 pages
Book Rating : 4.1/5 (18 download)

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Book Synopsis Systems Biology in Drug Discovery and Development by : Daniel L. Young

Download or read book Systems Biology in Drug Discovery and Development written by Daniel L. Young and published by John Wiley & Sons. This book was released on 2011-09-23 with total page 398 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first book to focus on comprehensive systems biology as applied to drug discovery and development Drawing on real-life examples, Systems Biology in Drug Discovery and Development presents practical applications of systems biology to the multiple phases of drug discovery and development. This book explains how the integration of knowledge from multiple sources, and the models that best represent that integration, inform the drug research processes that are most relevant to the pharmaceutical and biotechnology industries. The first book to focus on comprehensive systems biology and its applications in drug discovery and development, it offers comprehensive and multidisciplinary coverage of all phases of discovery and design, including target identification and validation, lead identification and optimization, and clinical trial design and execution, as well as the complementary systems approaches that make these processes more efficient. It also provides models for applying systems biology to pharmacokinetics, pharmacodynamics, and candidate biomarker identification. Introducing and explaining key methods and technical approaches to the use of comprehensive systems biology on drug development, the book addresses the challenges currently facing the pharmaceutical industry. As a result, it is essential reading for pharmaceutical and biotech scientists, pharmacologists, computational modelers, bioinformaticians, and graduate students in systems biology, pharmaceutical science, and other related fields.

Bioinformatics and Drug Discovery

Author : Richard S. Larson
Publisher :
ISBN 13 : 9781617799655
Total Pages : 374 pages
Book Rating : 4.7/5 (996 download)

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Book Synopsis Bioinformatics and Drug Discovery by : Richard S. Larson

Download or read book Bioinformatics and Drug Discovery written by Richard S. Larson and published by . This book was released on 2012 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent advances in drug discovery have been rapid. The second edition of Bioinformatics and Drug Discovery has been completely updated to include topics that range from new technologies in target identification, genomic analysis, cheminformatics, protein analysis, and network or pathway analysis. Each chapter provides an extended introduction that describes the theory and application of the technology. In the second part of each chapter, detailed procedures related to the use of these technologies and software have been incorporated. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Bioinformatics and Drug Discovery, Second Edition seeks to aid scientists in the further study of the rapidly expanding field of drug discovery.