Download or read book Disruption of Protein Protein Interfaces written by Stefano Mangani and published by Springer Science & Business Media. This book was released on 2013-06-28 with total page 167 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Disruption of Protein-Protein Interfaces" reviews the latest developments and future perspectives in drug discovery at protein-protein interfaces. The authors detail experimental and computational tools to tackle the subject and highlight the contribution of the Italian research community to the field. Evidence shows that blocking or modulating protein-protein interactions might lead to the development of useful new drugs. Consequently, in recent years great effort has been dedicated to unveiling the molecular details of protein-protein interfaces by structural techniques e.g. X-ray diffraction, NMR spectroscopy. This book, written and edited by leaders in the field, provides examples from the literature of successes and failures to develop drug-like molecules effective in interacting at protein-protein interfaces.
Download or read book Protein Interactions Computational Methods Analysis And Applications written by M Michael Gromiha and published by World Scientific. This book was released on 2020-03-05 with total page 424 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is indexed in Chemical Abstracts ServiceThe interactions of proteins with other molecules are important in many cellular activities. Investigations have been carried out to understand the recognition mechanism, identify the binding sites, analyze the the binding affinity of complexes, and study the influence of mutations on diseases. Protein interactions are also crucial in structure-based drug design.This book covers computational analysis of protein-protein, protein-nucleic acid and protein-ligand interactions and their applications. It provides up-to-date information and the latest developments from experts in the field, using illustrations to explain the key concepts and applications. This volume can serve as a single source on comparative studies of proteins interacting with proteins/DNAs/RNAs/carbohydrates and small molecules.
Download or read book Disruption of Protein protein Interfaces and Computational Mechanistic Studies written by Phillip Pierre Painter and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Research is nothing if not collaborative; computational chemists have a wide variety of tools available at their disposal and can greatly facilitate the progress of research beyond what is possible using only traditional synthetic techniques. On the whole, computational chemistry has steadily gained acceptance in the scientific community. Advantages include no purifications of intermediates, virtually no exposure to toxic chemicals in the laboratory, and (relatively) quick turnarounds. When modeling specific reactions, the difficulty arises in interpreting the Potential Energy Surface (PES) and building a predictive model of reactivity rather than exhaustively examining every possibility. The use of computers as a tool to aid the modern chemist is examined within these chapters and explored in the context of small molecule inhibitor design and Density Functional Theory (DFT) mechanistic studies. Section 1 - Design and synthesis of potential therapeutics The rationale design of new therapeutics is a key application of computational chemistry. The chapters within this section serve as an introduction to the potential applications and utility of these methods. Chapter 1: This chapter introduces the need for new antibiotics and the basics of the computational methods used in the following chapters. Chapter 2: The design and synthesis of potential bacterial cell division modulators is explored. The need for new antibiotics is readily documented in the literature as modern antibiotics form an evolutionary pressure. Understanding the mechanisms by which bacterial cells divide, and thus propagate, could lead to novel therapeutics. SulA naturally modulates the bacterial cell division protein FtsZ, and disrupting this interaction with a small molecule allows for study without the need for inducing a genetic mutation. Two inhibitor scaffolds for disrupting this protein interface were designed using the Openeye suite of programs. Additionally, the screening of large molecular libraries from the ZINC database was accomplished against both the SulA and FtsZ protein receptors, leading to identification of commercially available compounds that could be assayed against both protein targets. Chapter 3: The generation and screening of a novel library based on Gyramide A for LogD and other molecular descriptors from commercially available benzaldehydes and sulfonamides was accomplished. Section 2 -- Pericyclic reactions Pericyclic reactions allow for complex transformations of organic skeletons in a concerted fashion, thereby preserving stereochemical information. These reactions are not only relevant to the synthetic world, but are found in nature as well. Chapter 4: The [3,3] sigmatropic shift reaction, known as the Cope rearrangement, is explored. In the addition of alkynyl sulfones and tertiary amines, ring expansion is found to be dictated largely by steric considerations, while a lone pair on carbon acts largely as a substituent instead of a nucleophile. Chapter 5: A bio-mimetic variation of the Cope rearrangement utilizing Globiferin is explored. An intriguing catalytic effect was discovered when a protonated tertiary amine was used to try to find a stepwise pathway, but a concerted process with a substantially lower barrier for rearrangement was found instead, having a potentially substantial affect on our understanding of biosynthetic pathways. Chapter 6: The viability of Nitrone-Alkene (3+2) cyclizations is explored in the formation of Fluggine A. One of the reactants can undergo a competing (3+2) cyclization intramolecularly. However, this is found to have a higher barrier. This is consistent with the observation of Fluggine A formation when the required norsecurinine substrate is present, and cyclization with itself to form virosaine B when norsecurinine is absent. Section 3 -- Synthetic Collaborations/Heterocycle reactions The projects within this section are collaborations with synthetic groups at other universities and illustrate the utility in direct collaborations between computational chemists and other researchers. Each chapter in this section covers the formation of heterocycles, which are a privileged scaffold and known to possess biologically relevant activity. As such, the formation of new heterocycles is of great scientific interest. Chapter 7: Bryostatin 1 is of biological interest due to antitumor activity, and its complex chemical structure. The formation of tetrahydropyran analogs of bryostatin 1 derived via silyl-Prins cyclization is examined computationally in this chapter. The stabilization of a tertiary cation by a [beta]-silyl substituent is key for explaining the observed selectivity. Chapter 8: The possibility of a pericyclic six-electron electrocyclization in the formation of indolines is explored but found to be significantly higher than the comparable 5-endo-trig cyclization. The competing mechanisms were found to arise from different imine reactant geometries, allowing for different orbital alignments in their respective TS geometries. The cinchona alkaloids are found to affect enantioselectivity through more than a simple counter-ion effect. Chapter 9: This chapter describes a collaborative project between three academic groups -- specialists in synthetic methods, quantum chemical computations, and kinetic studies -- to reconcile differences in data obtained while studying a heterocycloisomerization reaction for the creation of annulated aminopyrroles. Through collaboration, a complete picture of the mechanism was obtained, which would have been insufficient/inadequate had any one research group been removed.
Download or read book Protein protein Recognition written by Colin Kleanthous and published by Frontiers in Molecular Biology. This book was released on 2000 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt: The purpose of Protein-Protein Recognition is to bring together concepts and systems pertaining to protein-protein interactions in a single unifying volume. In the light of the information from the genome sequencing projects and the increase in structural information it is an opportune time totry to make generalizations about how and why proteins form complexes with each other. The emphasis of the book is on heteromeric complexes (complexes in which each of the components can exist in an unbound state) and will use well-studied model systems to explain the processes of formingcomplexes. After an introductory section on the kinetics, thermodynamics, analysis, and classification of protein-protein interactions, weak, intermediate, and high affinity complexes are dealt with in turn. Weak affinity complexes are represented by electron transfer proteins and integrincomplexes. Anti-lysozyme antibodies, the MHC proteins and their interactions with T-cell receptors, and the protein interactions of eukaryotic signal transduction are the systems used to explain complexes with intermediate affinities. Finally, tight binding complexes are represented by theinteraction of protein inhibitors with serine proteases and by nuclease inhibitor complexes. Throughout the chapters common themes are the technologies which have had the greatest impact, how specificity is determined, how complexes are stabilized, and medical and industrial applications.
Download or read book Inhibitors of Protein Protein Interactions written by Ali Tavassoli and published by Royal Society of Chemistry. This book was released on 2020-12-07 with total page 357 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein-protein interactions (PPI) are at the heart of the majority of cellular processes, and are frequently dysregulated or usurped in disease. Given this central role, the inhibition of PPIs has been of significant interest as a means of treating a wide variety of diseases. However, there are inherent challenges in developing molecules capable of disrupting the relatively featureless and large interfacial areas involved. Despite this, there have been a number of successes in this field in recent years using both traditional drug discovery approaches and innovative, interdisciplinary strategies using novel chemical scaffolds. This book comprehensively covers the various aspects of PPI inhibition, encompassing small molecules, peptidomimetics, cyclic peptides, stapled peptides and macrocycles. Illustrated throughout with successful case studies, this book provides a holistic, cutting-edge view of the subject area and is ideal for chemical biologists and medicinal chemists interested in developing PPI inhibitors.
Download or read book Structural Biology in Drug Discovery written by Jean-Paul Renaud and published by John Wiley & Sons. This book was released on 2020-01-09 with total page 1367 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the most comprehensive and up-to-date overview of structure-based drug discovery covering both experimental and computational approaches, Structural Biology in Drug Discovery: Methods, Techniques, and Practices describes principles, methods, applications, and emerging paradigms of structural biology as a tool for more efficient drug development. Coverage includes successful examples, academic and industry insights, novel concepts, and advances in a rapidly evolving field. The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a valuable reference and resource that: Presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology Includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design Emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures Illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins
Download or read book Protein Protein Interactions written by Weibo Cai and published by BoD – Books on Demand. This book was released on 2012-03-30 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins are indispensable players in virtually all biological events. The functions of proteins are coordinated through intricate regulatory networks of transient protein-protein interactions (PPIs). To predict and/or study PPIs, a wide variety of techniques have been developed over the last several decades. Many in vitro and in vivo assays have been implemented to explore the mechanism of these ubiquitous interactions. However, despite significant advances in these experimental approaches, many limitations exist such as false-positives/false-negatives, difficulty in obtaining crystal structures of proteins, challenges in the detection of transient PPI, among others. To overcome these limitations, many computational approaches have been developed which are becoming increasingly widely used to facilitate the investigation of PPIs. This book has gathered an ensemble of experts in the field, in 22 chapters, which have been broadly categorized into Computational Approaches, Experimental Approaches, and Others.
Download or read book Protein protein Complexes written by Martin Zacharias and published by World Scientific. This book was released on 2010 with total page 401 pages. Available in PDF, EPUB and Kindle. Book excerpt: Given the immense progress achieved in elucidating protein-protein complex structures and in the field of protein interaction modeling, there is great demand for a book that gives interested researchers/students a comprehensive overview of the field. This book does just that. It focuses on what can be learned about protein-protein interactions from the analysis of protein-protein complex structures and interfaces. What are the driving forces for protein-protein association? How can we extract the mechanism of specific recognition from studying protein-protein interfaces? How can this knowledge be used to predict and design protein-protein interactions (interaction regions and complex structures)? What methods are currently employed to design protein-protein interactions, and how can we influence protein-protein interactions by mutagenesis and small-molecule drugs or peptide mimetics?The book consists of about 15 review chapters, written by experts, on the characterization of protein-protein interfaces, structure determination of protein complexes (by NMR and X-ray), theory of protein-protein binding, dynamics of protein interfaces, bioinformatics methods to predict interaction regions, and prediction of protein-protein complex structures (docking and homology modeling of complexes, etc.) and design of protein-protein interactions. It serves as a bridge between studying/analyzing protein-protein complex structures (interfaces), predicting interactions, and influencing/designing interactions.
Download or read book Protein Protein and Domain Domain Interactions written by Pandjassarame Kangueane and published by Springer. This book was released on 2018-02-16 with total page 216 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book illustrates the importance and significance of the molecular (physical and chemical) and evolutionary (gene fusion) principles of protein-protein and domain-domain interactions towards the understanding of cell division, disease mechanism and target definition in drug discovery. It describes the complex issues associated with this phenomenon using cutting edge advancement in Bioinformatics and Bioinformation Discovery. The chapters provide current information pertaining to the types of protein-protein complexes (homodimers, heterodimers, multimer complexes) in context with various specific and sensitive biological functions. The significance of such complex formation in human biology in the light of molecular evolution is also highlighted using several examples. The chapters also describe recent advancements on the molecular principles of protein-protein interaction with reference to evolution towards target identification in drug discovery. Finally, the book also elucidates a comprehensive yet a representative description of a large number of challenges associated with the molecular interaction of proteins.
Download or read book Protein protein Complexes written by Martin Zacharias and published by World Scientific. This book was released on 2010 with total page 401 pages. Available in PDF, EPUB and Kindle. Book excerpt: Given the immense progress achieved in elucidating protein-protein complex structures and in the field of protein interaction modeling, there is great demand for a book that gives interested researchers/students a comprehensive overview of the field. This book does just that. It focuses on what can be learned about protein-protein interactions from the analysis of protein-protein complex structures and interfaces. What are the driving forces for protein-protein association? How can we extract the mechanism of specific recognition from studying protein-protein interfaces? How can this knowledge be used to predict and design protein-protein interactions (interaction regions and complex structures)? What methods are currently employed to design protein-protein interactions, and how can we influence protein-protein interactions by mutagenesis and small-molecule drugs or peptide mimetics?The book consists of about 15 review chapters, written by experts, on the characterization of protein-protein interfaces, structure determination of protein complexes (by NMR and X-ray), theory of protein-protein binding, dynamics of protein interfaces, bioinformatics methods to predict interaction regions, and prediction of protein-protein complex structures (docking and homology modeling of complexes, etc.) and design of protein-protein interactions. It serves as a bridge between studying/analyzing protein-protein complex structures (interfaces), predicting interactions, and influencing/designing interactions.
Download or read book Molecular Interaction Fields written by Gabriele Cruciani and published by John Wiley & Sons. This book was released on 2006-05-12 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: This unique reference source, edited by the world's most respected expert on molecular interaction field software, covers all relevant principles of the GRID force field and its applications in medicinal chemistry. Entire chapters on 3D-QSAR, pharmacophore searches, docking studies, metabolism predictions and protein selectivity studies, among others, offer a concise overview of this emerging field. As an added bonus, this handbook includes a CD-ROM with the latest commercial versions of the GRID program and related software.
Download or read book Protein Instability at Interfaces During Drug Product Development written by Jinjiang Li and published by Springer Nature. This book was released on 2021-02-12 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins are exposed to various interfacial stresses during drug product development. They are subjected to air-liquid, liquid-solid, and, sometimes, liquid-liquid interfaces throughout the development cycle-from manufacturing of drug substances to storage and drug delivery. Unlike small molecule drugs, proteins are typically unstable at interfaces where, on adsorption, they often denature and form aggregates, resulting in loss of efficacy and potential immunogenicity. This book covers both the fundamental aspects of proteins at interfaces and the quantification of interfacial behaviors of proteins. Importantly, this book introduces the industrial aspects of protein instabilities at interfaces, including the processes that introduce new interfaces, evaluation of interfacial instabilities, and mitigation strategies. The audience that this book targets encompasses scientists in the pharmaceutical and biotech industry, as well as faculty and students from academia in the surface science, pharmaceutical, and medicinal chemistry areas.
Download or read book Gene Regulatory Effects of Protein Interface Disruption in the CBF Complex written by Jeanna Sheen and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins perform their roles in the cell through interactions--with DNA, with other proteins, or with other molecular substrates. Protein-protein interactions are especially important during the regulation of transcription, as many transcription factors come together to bind to each other and to DNA to form a transcriptional complex. Mutations can disrupt these interactions, leading to abnormal gene regulation, expression, and possibly disease. Here, we analyze the 3D structure of the core binding factor (CBF) complex to create a library of mutations for its subunits CBFB and RUNX1. We use ScalablE fUnctional Screening by Sequencing (SEUSS) to study the effects of the RUNX1 library in myelogenous leukemia K562 cells using single cell RNA sequencing. We then further investigate the effects of selected RUNX1 mutations on chromatin accessibility and gene expression using bulk ATAC and RNA sequencing. We find that our library design was able to select mutations that perturbed interfaces of the complex, resulting in loss of function-like and hypomorphic phenotypes with effects on distinct cellular pathways. Our bulk ATAC and RNA sequencing analysis reveals enrichment of RUNX1 binding in accessible DNA regions associated with regulation of differentially expressed genes. Our work shows the potential of targeting the binding interfaces of a protein to gain insight into how disruption of its function may cause downstream effects in the cell.
Download or read book Protein Protein Interactions written by Michael D. Wendt and published by Springer Science & Business Media. This book was released on 2012-06-26 with total page 276 pages. Available in PDF, EPUB and Kindle. Book excerpt: Michael D. Wendt Protein-Protein Interactions as Drug Targets Shaomeng Wang , Yujun Zhao , Denzil Bernard , Angelo Aguilar , Sanjeev Kumar Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapeutics Kurt Deshayes , Jeremy Murray , Domagoj Vucic The Development of Small-Molecule IAP Antagonists for the Treatment of Cancer John F. Kadow , David R. Langley , Nicholas A. Meanwell , Michael A. Walker , Kap-Sun Yeung , Richard Pracitto Protein-Protein Interaction Targets to Inhibit HIV-1 Infection Nicholas A. Meanwell , David R. Langley Inhibitors of Protein-Protein Interactions in Paramyxovirus Fusion – a Focus on Respiratory Syncytial Virus Andrew B. Mahon , Stephen E. Miller , Stephen T. Joy , Paramjit S. Arora Rational Design Strategies for Developing Synthetic Inhibitors of Helical Protein Interfaces Michael D. Wendt The Discovery of Navitoclax, a Bcl-2 Family Inhibitor
Download or read book Fuzziness written by Monika Fuxreiter and published by Springer Science & Business Media. This book was released on 2012-03-07 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: Detailed characterization of fuzzy interactions will be of central importance for understanding the diverse biological functions of intrinsically disordered proteins in complex eukaryotic signaling networks. In this volume, Peter Tompa and Monika Fuxreiter have assembled a series of papers that address the issue of fuzziness in molecular interactions. These papers provide a broad overview of the phenomenon of fuzziness and provide compelling examples of the central role played by fuzzy interactions in regulation of cellular signaling processes and in viral infectivity. These contributions summarize the current state of knowledge in this new field and will undoubtedly stimulate future research that will further advance our understanding of fuzziness and its role in biomolecular interactions.
Download or read book Principles of Protein Protein Association written by Harold P. Erickson and published by IOP Publishing Limited. This book was released on 2019-06-19 with total page 100 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein-protein associations are fundamental to biological mechanisms. This book, created from lecture notes and classroom sessions, covers the general principles of protein-protein association. It should be of considerable value to cell biologists with a limited understanding of proteins, as well as to biochemists with a deeper background in protein structure. Developed from lectures given to beginning graduate students in cell and molecular biology, Principles of Protein-Protein Association presents general principles of thermodynamics and kinetics, and structural principles of protein-protein interface. An important feature is guided reading of informative classic papers. Faculties organizing similar classes, and students and researchers wishing to learn on their own, will also find this book of use. Book jacket.
Download or read book Protein Nanoparticle Interactions written by Masoud Rahman and published by Springer Science & Business Media. This book was released on 2013-06-24 with total page 95 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, the fabrication of nanomaterials and exploration of their properties have attracted the attention of various scientific disciplines such as biology, physics, chemistry, and engineering. Although nanoparticulate systems are of significant interest in various scientific and technological areas, there is little known about the safety of these nanoscale objects. It has now been established that the surfaces of nanoparticles are immediately covered by biomolecules (e.g. proteins, ions, and enzymes) upon their entrance into a biological medium. This interaction with the biological medium modulates the surface of the nanoparticles, conferring a “biological identity” to their surfaces (referred to as a “corona”), which determines the subsequent cellular/tissue responses. The new interface between the nanoparticles and the biological medium/proteins, called “bio-nano interface,” has been very rarely studied in detail to date, though the interest in this topic is rapidly growing. In this book, the importance of the physiochemical characteristics of nanoparticles for the properties of the protein corona is discussed in detail, followed by comprehensive descriptions of the methods for assessing the protein-nanoparticle interactions. The advantages and limitations of available corona evaluation methods (e.g. spectroscopy methods, mass spectrometry, nuclear magnetic resonance, electron microscopy, X-ray crystallography, and differential centrifugal sedimentation) are examined in detail, followed by a discussion of the possibilities for enhancing the current methods and a call for new techniques. Moreover, the advantages and disadvantages of protein-nanoparticle interaction phenomena are explored and discussed, with a focus on the biological impacts.
