Download or read book Protein Ligand Binding Thermodynamics written by Justin M. Miller and published by American Chemical Society. This book was released on 2023-06-01 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ligand binding by macromolecules represents a core event of broad relevance to a range of systems, including catalytic systems alongside noncatalytic systems such as nucleic acid binding by transcription factors or extracellular ligand binding by proteins involved in signaling pathways. The scope of this primer is constrained to introduce only foundational models without significant discussion of more advanced topics such as allosteric or linkage effects. Linkage occurs when the binding of a ligand is influenced by the binding of another molecule of the same ligand (homotropic linkage), the binding of a different ligand (heterotropic linkage), physical variables such as temperature or pressure (physical linkage), or changes in macromolecular assembly state (polysteric linkage). Taking this into account, the foundational themes presented in this primer can be used to describe any macromolecule–ligand interaction either by direct use of the models and techniques described here or by applying them to develop more advanced models to explain additional complexities such as those allosteric or linkage effects just mentioned. The target audience of this primer is the senior undergraduate or junior graduate student who lacks a foundation in ligand-binding thermodynamics. As such, we have focused primarily on foundational thermodynamic treatments and presented only general discussions of relevant experimental designs. Readers of this primer will learn how to build a working understanding of common factors that promote energetic favorability for ligand binding; develop a functional toolbox to understand ligand binding from the perspective of collecting, plotting, and interpreting ligand-binding data; enhance proficiency in deriving thermodynamic mechanisms for ligand binding; and become comfortable in interpreting binding data reported in the literature and independently expanding knowledge beyond the scope introduced in this primer.

Download or read book Protein Ligand Interactions written by Holger Gohlke and published by John Wiley & Sons. This book was released on 2012-05-21 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: Innovative and forward-looking, this volume focuses on recent achievements in this rapidly progressing field and looks at future potential for development. The first part provides a basic understanding of the factors governing protein-ligand interactions, followed by a comparison of key experimental methods (calorimetry, surface plasmon resonance, NMR) used in generating interaction data. The second half of the book is devoted to insilico methods of modeling and predicting molecular recognition and binding, ranging from first principles-based to approximate ones. Here, as elsewhere in the book, emphasis is placed on novel approaches and recent improvements to established methods. The final part looks at unresolved challenges, and the strategies to address them. With the content relevant for all drug classes and therapeutic fields, this is an inspiring and often-consulted guide to the complexity of protein-ligand interaction modeling and analysis for both novices and experts.

Download or read book Protein Ligand Interactions written by Hans-Joachim Böhm and published by John Wiley & Sons. This book was released on 2006-03-06 with total page 262 pages. Available in PDF, EPUB and Kindle. Book excerpt: The lock-and-key principle formulated by Emil Fischer as early as the end of the 19th century has still not lost any of its significance for the life sciences. The basic aspects of ligand-protein interaction may be summarized under the term 'molecular recognition' and concern the specificity as well as stability of ligand binding. Molecular recognition is thus a central topic in the development of active substances, since stability and specificity determine whether a substance can be used as a drug. Nowadays, computer-aided prediction and intelligent molecular design make a large contribution to the constant search for, e. g., improved enzyme inhibitors, and new concepts such as that of pharmacophores are being developed. An up-to-date presentation of an eternally young topic, this book is an indispensable information source for chemists, biochemists and pharmacologists dealing with the binding of ligands to proteins.

Download or read book Microcalorimetry of Biological Molecules written by Eric Ennifar and published by Humana. This book was released on 2019-04-01 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides methods on microcalorimetry approaches to investigate complex biological molecular systems. Chapters guide readers through Differential Scanning Calorimetry (DSC), Isothermal Titration Calorimetry (ITC), and advanced data processing. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Microcalorimetry of Biological Molecules: Methods and Protocols aims to ensure successful results in the further study of this vital field.

Download or read book Protein Ligand Interactions written by Mark A. Williams and published by Humana. This book was released on 2016-11-17 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Proteins are the cell’s workers, their messengers and overseers. In these roles, proteins specifically bind small molecules, nucleic acid and other protein partners. Cellular systems are closely regulated and biologically significant changes in populations of particular protein complexes correspond to very small variations of their thermodynamics or kinetics of reaction. Interfering with the interactions of proteins is the dominant strategy in the development of new pharmaceuticals. Protein Ligand Interactions: Methods and Applications, Second Edition provides a complete introduction to common and emerging procedures for characterizing the interactions of individual proteins. From the initial discovery of natural substrates or potential drug leads, to the detailed quantitative understanding of the mechanism of interaction, all stages of the research process are covered with a focus on those techniques that are, or are anticipated to become, widely accessible and performable with mainstream commercial instrumentation. Written in the highly successful Methods in Molecular Biology series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Protein Ligand Interactions: Methods and Applications, Second Edition serves as an ideal guide for researchers new to the field of biophysical characterization of protein interactions – whether they are beginning graduate students or experts in allied areas of molecular cell biology, microbiology, pharmacology, medicinal chemistry or structural biology.

Download or read book Fragment Based Drug Discovery written by Steven Howard and published by Royal Society of Chemistry. This book was released on 2015-06-17 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: Fragment-based drug discovery is a rapidly evolving area of research, which has recently seen new applications in areas such as epigenetics, GPCRs and the identification of novel allosteric binding pockets. The first fragment-derived drug was recently approved for the treatment of melanoma. It is hoped that this approval is just the beginning of the many drugs yet to be discovered using this fascinating technique. This book is written from a Chemist's perspective and comprehensively assesses the impact of fragment-based drug discovery on a wide variety of areas of medicinal chemistry. It will prove to be an invaluable resource for medicinal chemists working in academia and industry, as well as anyone interested in novel drug discovery techniques.

Download or read book COMPUTATIONAL APPROACHES FOR PROTEIN FOLDING AND LIGAND BINDING written by Si Zhang and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The cellular function of proteins, and their targeting by drug applications, are both governed by biomolecular thermodynamics and kinetics. In order to make meaningful and efficient predictions of these mechanisms, molecular simulations must be able to estimate the binding affinity and rates of association and dissociation of a protein-ligand complex, or the populations and rates of exchange between distinct conformational states (i.e. folding and unfolding, binding and unbinding). The above studies are typically done using different, but complementary approaches. Alchemical methods, including free energy perturbation (FEP) and thermodynamic integration (TI), have become the dominant method for computing high-quality estimates of protein-ligand binding free energies. In particular, the widely-used approach of relative binding free energy calculation can deliver accuracies within 1 kcal mol−1. However, detailed physical pathways and kinetics are missing from these calculations. In principle, all-atom molecular dynamics (MD) simulation, with the help of Markov State Models (MSMs), can be used to obtain this information, yet finite sampling error still limits MSM approaches from making accurate predictions for very slow unfolding or unbinding processes. To overcome these issues, a new approach called multiensemble Markov models (MEMMs) have been developed, in which sampling from biased thermodynamic ensembles can be used to infer states populations and transition rates in unbiased ensembles. In this dissertation, two distinct biophysical problems are investigated. In the first part, we apply expanded ensemble (EE) methods to accurately predict relative binding free energies for a series of protein-ligand systems. Moreover, we propose a simple optimization scheme for choosing alchemical intermediates in free energy simulations. In the second part, we employ MEMMs to estimate the free energies and kinetics of protein folding and ligand binding, to achieve greatly improved predictions. Finally, we combine the above EE method and a maximum-caliber algorithm to study how sequence mutations perturb protein stability and folding kinetics. In summary, this work comprises a wide range of current methodology in biophysical simulation, complementing and improving upon existing approaches.

Download or read book Thermodynamics and Kinetics of Drug Binding written by György Keserü and published by John Wiley & Sons. This book was released on 2015-08-17 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: This practical reference for medicinal and pharmaceutical chemists combines the theoretical background with modern methods as well as applications from recent lead finding and optimization projects. Divided into two parts on the thermodynamics and kinetics of drug-receptor interaction, the text provides the conceptual and methodological basis for characterizing binding mechanisms for drugs and other bioactive molecules. It covers all currently used methods, from experimental approaches, such as ITC or SPR, right up to the latest computational methods. Case studies of real-life lead or drug development projects are also included so readers can apply the methods learned to their own projects. Finally, the benefits of a thorough binding mode analysis for any drug development project are summarized in an outlook chapter written by the editors.

Download or read book Multivalency written by Jurriaan Huskens and published by John Wiley & Sons. This book was released on 2018-02-05 with total page 434 pages. Available in PDF, EPUB and Kindle. Book excerpt: Connects fundamental knowledge of multivalent interactions with current practice and state-of-the-art applications Multivalency is a widespread phenomenon, with applications spanning supramolecular chemistry, materials chemistry, pharmaceutical chemistry and biochemistry. This advanced textbook provides students and junior scientists with an excellent introduction to the fundamentals of multivalent interactions, whilst expanding the knowledge of experienced researchers in the field. Multivalency: Concepts, Research & Applications is divided into three parts. Part one provides background knowledge on various aspects of multivalency and cooperativity and presents practical methods for their study. Fundamental aspects such as thermodynamics, kinetics and the principle of effective molarity are described, and characterisation methods, experimental methodologies and data treatment methods are also discussed. Parts two and three provide an overview of current systems in which multivalency plays an important role in chemistry and biology, with a focus on the design rules, underlying chemistry and the fundamental principles of multivalency. The systems covered range from chemical/materials-based ones such as dendrimers and sensors, to biological systems including cell recognition and protein binding. Examples and case studies from biochemistry/bioorganic chemistry as well as synthetic systems feature throughout the book. Introduces students and young scientists to the field of multivalent interactions and assists experienced researchers utilising the methodologies in their work Features examples and case studies from biochemistry/bioorganic chemistry, as well as synthetic systems throughout the book Edited by leading experts in the field with contributions from established scientists Multivalency: Concepts, Research & Applications is recommended for graduate students and junior scientists in supramolecular chemistry and related fields, looking for an introduction to multivalent interactions. It is also highly useful to experienced academics and scientists in industry working on research relating to multivalent and cooperative systems in supramolecular chemistry, organic chemistry, pharmaceutical chemistry, chemical biology, biochemistry, materials science and nanotechnology.

Download or read book Biomolecular Thermodynamics written by Douglas Barrick and published by CRC Press. This book was released on 2017-09-11 with total page 553 pages. Available in PDF, EPUB and Kindle. Book excerpt: "an impressive text that addresses a glaring gap in the teaching of physical chemistry, being specifically focused on biologically-relevant systems along with a practical focus.... the ample problems and tutorials throughout are much appreciated." –Tobin R. Sosnick, Professor and Chair of Biochemistry and Molecular Biology, University of Chicago "Presents both the concepts and equations associated with statistical thermodynamics in a unique way that is at visual, intuitive, and rigorous. This approach will greatly benefit students at all levels." –Vijay S. Pande, Henry Dreyfus Professor of Chemistry, Stanford University "a masterful tour de force.... Barrick's rigor and scholarship come through in every chapter." –Rohit V. Pappu, Edwin H. Murty Professor of Engineering, Washington University in St. Louis This book provides a comprehensive, contemporary introduction to developing a quantitative understanding of how biological macromolecules behave using classical and statistical thermodynamics. The author focuses on practical skills needed to apply the underlying equations in real life examples. The text develops mechanistic models, showing how they connect to thermodynamic observables, presenting simulations of thermodynamic behavior, and analyzing experimental data. The reader is presented with plenty of exercises and problems to facilitate hands-on learning through mathematical simulation. Douglas E. Barrick is a professor in the Department of Biophysics at Johns Hopkins University. He earned his Ph.D. in biochemistry from Stanford University, and a Ph.D. in biophysics and structural biology from the University of Oregon.

Download or read book Thermodynamics and Kinetics of Drug Binding written by György Keserü and published by John Wiley & Sons. This book was released on 2015-07-28 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: This practical reference for medicinal and pharmaceutical chemists combines the theoretical background with modern methods as well as applications from recent lead finding and optimization projects. Divided into two parts on the thermodynamics and kinetics of drug-receptor interaction, the text provides the conceptual and methodological basis for characterizing binding mechanisms for drugs and other bioactive molecules. It covers all currently used methods, from experimental approaches, such as ITC or SPR, right up to the latest computational methods. Case studies of real-life lead or drug development projects are also included so readers can apply the methods learned to their own projects. Finally, the benefits of a thorough binding mode analysis for any drug development project are summarized in an outlook chapter written by the editors.

Download or read book Mechanisms thermodynamics and kinetics of ligand binding revealed from molecular simulations and machine learning written by Yinglong Miao and published by Frontiers Media SA. This book was released on 2023-02-24 with total page 179 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Structure based Drug Design written by John E. Ladbury and published by Landes Bioscience. This book was released on 1997 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Dynamics and Thermodynamics of Protein ligand Interactions written by Richard William Malham and published by . This book was released on 2012 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt: Complex networks of protein-ligand interactions underpin cellular function and communication. Disease can arise from disruption of these networks through the alteration of protein-ligand interaction affinities, for example by protein mutation or ligand modification. Understanding the mechanisms and principles that define affinity is therefore critical to both understanding and engineering biomolecular interactions, e.g. optimising drug molecules to interact effectively with their biomolecular targets. Thermodynamics reveals that affinity can be expressed in terms of the Gibbs free energy change upon interaction. In turn, this is composed of enthalpic and entropic terms, which can be thought of loosely as arising from structural and dynamic factors respectively. Though enthalpic terms can be estimated to a reasonable degree using structural data, a better understanding of entropic contributions from dynamic processes is required. The mouse major urinary protein (MUP) has been successfully established as a model system to investigate the thermodynamics of protein-ligand interactions. This work uses MUP, and employs a wide range of biophysical techniques, to develop our understanding of the dynamic factors in the thermodynamics of protein-ligand interactions. Four factors are addressed. Protein solvation is addressed by investigating proposed entropic solvation of the MUP binding pocket, and the possibility of engineering a new binding profile through manipulation of sidechains and solvation in the binding pocket. Ligand conformational entropy is addressed by performing the first systematic assessment of the widely predicted, yet inconsistently observed, benefits of removing and restricting ligand bonds. The greatest entropic loss upon binding, that of ligand rotational and translational entropy, is addressed by assessing MD predictions of significant residual translation and rotational motion of IBMP bound to MUP. This is achieved by using a combination of NMR techniques. Finally, protein dynamics are addressed by undertaking a preliminary investigation of a potentially promising novel technique for probing site-specific changes in protein dynamics upon ligand binding.

Download or read book Reversible Ligand Binding written by Andrea Bellelli and published by John Wiley & Sons. This book was released on 2018-01-09 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: Presents the physical background of ligand binding and instructs on how experiments should be designed and analyzed Reversible Ligand Binding: Theory and Experiment discusses the physical background of protein-ligand interactions—providing a comprehensive view of the various biochemical considerations that govern reversible, as well as irreversible, ligand binding. Special consideration is devoted to enzymology, a field usually treated separately from ligand binding, but actually governed by identical thermodynamic relationships. Attention is given to the design of the experiment, which aids in showing clear evidence of biochemical features that may otherwise escape notice. Classical experiments are reviewed in order to further highlight the importance of the design of the experiment. Overall, the book supplies students with the understanding that is necessary for interpreting ligand binding experiments, formulating plausible reaction schemes, and analyzing the data according to the chosen model(s). Topics covered include: theory of ligand binding to monomeric proteins; practical considerations and commonly encountered problems; oligomeric proteins with multiple binding sites; ligand binding kinetics; hemoglobin and its ligands; single-substrate enzymes and their inhibitors; two-substrate enzymes and their inhibitors; and rapid kinetic methods for studying enzyme reactions. Bridges theory of ligand binding and allostery with experiments Applies historical and physical insight to provide a clear understanding of ligand binding Written by a renowned author with long-standing research and teaching expertise in the area of ligand binding and allostery Based on FEBS Advanced Course lectures on the topic Reversible Ligand Binding: Theory and Experiment is an ideal text reference for students and scientists involved in biophysical chemistry, physical biochemistry, biophysics, molecular biology, protein engineering, drug design, pharmacology, physiology, biotechnology, and bioengineering.

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 Free Energy Calculations written by Christophe Chipot and published by Springer Science & Business Media. This book was released on 2007-01-08 with total page 528 pages. Available in PDF, EPUB and Kindle. Book excerpt: Free energy constitutes the most important thermodynamic quantity to understand how chemical species recognize each other, associate or react. Examples of problems in which knowledge of the underlying free energy behaviour is required, include conformational equilibria and molecular association, partitioning between immiscible liquids, receptor-drug interaction, protein-protein and protein-DNA association, and protein stability. This volume sets out to present a coherent and comprehensive account of the concepts that underlie different approaches devised for the determination of free energies. The reader will gain the necessary insight into the theoretical and computational foundations of the subject and will be presented with relevant applications from molecular-level modelling and simulations of chemical and biological systems. Both formally accurate and approximate methods are covered using both classical and quantum mechanical descriptions. A central theme of the book is that the wide variety of free energy calculation techniques available today can be understood as different implementations of a few basic principles. The book is aimed at a broad readership of graduate students and researchers having a background in chemistry, physics, engineering and physical biology.