Integrative Modeling of Function-associated Molecular Recognition in Protein-ligand, Protein-peptide, and Protein-protein Complexes PDF Download
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Author: Benedikt Frieg
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Benedikt Frieg
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Hans-Joachim Böhm
Publisher: John Wiley & Sons
ISBN: 3527605517
Category : Science
Languages : en
Pages : 262
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Book Description
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.
Author: Holger Gohlke
Publisher: John Wiley & Sons
ISBN: 3527645977
Category : Medical
Languages : en
Pages : 359
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Book Description
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.
Author:
Publisher: Elsevier
ISBN: 0080493750
Category : Science
Languages : en
Pages : 343
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Book Description
Protein modules engage in a multitude of interactions with one another and with other cellular components, notably with DNA. These interactions are a central aspect of protein function of great relevance in the post-genomic era. This volume describes a panel of approaches for analyzing protein modules and their interactions, ranging from bioinformatics to physical chemistry, to biochemistry, with an emphasis on the structure-function relationship in protein-protein complexes involved in cellular processes including signal transduction. Comprehensive overview of different facets of macromolecule interactions Computational and bioinformatics aspects of analyzing protein modules and their interactions Emphasis on structure-function relationship in protein-protein complexes involved in cellular processes
Author: Martin Zacharias
Publisher: World Scientific
ISBN: 1848163401
Category : Medical
Languages : en
Pages : 401
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Book Description
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, etcetera.) 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.
Author: Andrey Dyachenko
Publisher:
ISBN:
Category :
Languages : en
Pages : 163
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Book Description
In the present thesis we have explored different factors that impede accurate quantitative description of non-covalent protein-protein and protein-ligand interactions and design of new potent and specific binders from the scratch. Firstly, we addressed the role of solvent in the mechanism of non-covalent interactions. Secondly, we tackled the question about the intrinsic conformational flexibility of the protein molecules and the part it plays in weak interactions between proteins. In the first part of the thesis we studied the interactions of vascular endothelial growth factor (VEGF) protein with five cyclic peptides in solution and gas phase. The results showed that affinities of five ligands to VEGF in solution and gas phase are ranked in inversed order. That is, the that has the highest affinity in solution (as shown by chemical shift perturbation NMR and isothermal titration calorimetry) forms the weakest complex with VEGF in gas phase, and vice versa. We compared gas-phase and solution binding affinities of of five peptides and made qualitative conclusions about the role of the solvent in protein-ligand interactions. In order to obtain more quantitative information about the gas-phase behavior of non-covalent complexes we have developed a combined experimental/theoretical approach to study the energetics of collisional activation of the ion prior to dissociation. We applied developed strategy to model CID in traveling wave ion guide (TWIG) collision cell. We validated the model on the CID of leu-enkephalin peptide and then applied developed strategy to five non-covalent protein-peptide complexes and found activation energies of their dissociation reactions. Next we applied ESI native MS to study the allosteric interactions between the molecular chaperonin GroEL and ATP. The obtained data allowed to construct a scheme of conformational transition of GroEL upon binding of ATP and distinguish between two different cooperativity models, providing strong arguments in favor of Monod-Wyman-Changeux (MWC) model. Finally, be studied the backbone dynamics of VEGF with a combination of NMR relaxation and all-atom force-field based normal mode analysis (NMA). We showed that combination of experimental and computational approach allows to identify flexible zones with higher level of confidence. We also found out that residues, that are involved VEGF-receptor interactions, reside in or close to the flexible zones, suggesting the critical role conformational plasticity plays in the non-covalent protein-protein interactions.
Author: M Michael Gromiha
Publisher: World Scientific
ISBN: 9811211884
Category : Science
Languages : en
Pages : 424
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Book Description
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.
Author: Ying Xu
Publisher: Springer Science & Business Media
ISBN: 0387688250
Category : Science
Languages : en
Pages : 335
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Book Description
Volume Two of this two-volume sequence presents a comprehensive overview of protein structure prediction methods and includes protein threading, De novo methods, applications to membrane proteins and protein complexes, structure-based drug design, as well as structure prediction as a systems problem. A series of appendices review the biological and chemical basics related to protein structure, computer science for structural informatics, and prerequisite mathematics and statistics.
Author: Irena Roterman-Konieczna
Publisher: Springer Science & Business Media
ISBN: 9400752857
Category : Medical
Languages : en
Pages : 173
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Book Description
This volume presents a review of the latest numerical techniques used to identify ligand binding and protein complexation sites. It should be noted that there are many other theoretical studies devoted to predicting the activity of specific proteins and that useful protein data can be found in numerous databases. The aim of advanced computational techniques is to identify the active sites in specific proteins and moreover to suggest a generalized mechanism by which such protein-ligand (or protein-protein) interactions can be effected. Developing such tools is not an easy task – it requires extensive expertise in the area of molecular biology as well as a firm grasp of numerical modeling methods. Thus, it is often viewed as a prime candidate for interdisciplinary research.
Author: Wanli You
Publisher:
ISBN: 9780355471953
Category : Cheminformatics
Languages : en
Pages : 262
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Book Description
Molecular recognition is fundamentally important in biological chemistry. Nowadays, with the rapid development of computational technology and algorithm, molecular modeling has become a powerful tool in studying molecular recognition, such as exploring molecular interactions and understanding biological dynamic processes, making significant contributions to modern biology and drug discovery. The state-of-the-art techniques of computational chemistry and molecular modeling can be applied to study a wide range of chemical and biological systems of interest. This enables us to study structural details at the atomic level and obtain chemical/biological information which is not available by experimental measurements. This dissertation project focused on modeling the recognition mechanisms of biomolecules and their conjugated ligands. Multiple computational techniques, such as molecular dynamics simulation, enhanced sampling methods and free energy calculation were applied. The model systems included signaling domains (BRCT domain), kinase (p38 kinase), enzyme system (TRPS) and small biomolecular system (cyclodextrin). The details of protein-ligand interactions, including both enthalpic and entropic contribution within protein domain-phosphopeptide systems were investigated, based on which new inhibitors were proposed. Several enhanced sampling methods like accelerated molecular dynamics simulation, pathway search guided by internal motions (PSIM) and umbrella sampling, were applied to explore the dissociation pathway of kinase-ligand systems and the motions of kinase during dissociation process were studied both thermodynamically and kinetically, protein conformational rearrangement was found to differentiate slow and fast unbinding inhibitors, casting light on high efficacy inhibitor design. Furthermore, using full structural molecular modeling, we explored how the position of a single proton can change the overall protein dynamics and further activate or inactivate enzyme catalysis, elucidating the catalytic mechanism of TRPS. In addition, we performed systematically evaluation to the performance of umbrella sampling, investigated the influence of subtle changes in the dissociation pathways and conformational sampling methods that provide the initial conformations, paving way for future improvement of umbrella sampling. This project studies the details of receptor-ligand interaction and provides a more complete picture of molecular recognition.
