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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: M Michael Gromiha
Publisher: World Scientific
ISBN: 9811211884
Category : Science
Languages : en
Pages : 424
Get Book Here
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: Benjamin Michael Samudio
Publisher:
ISBN: 9781369201079
Category :
Languages : en
Pages :
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Book Description
Proteins are fascinating biomolecular "machines" that enable the chemistry of life to occur. They underlie such diverse processes as energy transduction and immunity. Science continuous to unravel how these proteins work and many exciting questions remain to be answered. A paramount goal in the study of proteins is the understanding of how protein structure and dynamics facilitate chemistry. Proteins undergo conformational changes which make certain chemistry more probable. Elucidating these conformational changes is a major challenge to which both experimental and computational methods are applied. Computational methods can complement experimental ones by modeling protein conformational changes at an atomic level of detail. In addition, more elaborate computational methods can model chemical changes and reactions. This provides a link between structure and chemistry which is central to descriptions of protein function. This dissertation describes my research involving proteins which has been carried out at two institutions, the University of California in Davis (UC Davis) and the Novartis Institutes for Biomedical Research (NIBR), and correspondingly is divided into two parts. Part I: Unidirectional Proton Translocation Involving Glu-242 of Cytochrome c Oxidase (UC Davis) Cytochrome c oxidase (CcO) is the fourth protein complex in the electron transport chain (ETC) of mitochondria and some bacteria. This protein is embedded within the proton impermeable inner membrane of mitochondria and outer membrane in bacteria. CcO functions to: 1) reduce dioxygen to water and 2) move protons in a scalar manner from a lower concentration of protons in the mitochondrial matrix to a higher concentration of protons in the intermembrane space in a process known as proton pumping. Proton pumping establishes an electrochemical gradient across the inner membrane which is essential to aerobic life. CcO is remarkable because it is able to pump protons against the electrochemical gradient via a thermodynamically unfavorable but unidirectional and productive trajectory. CcO is unique as of this writing, in that it is designated as a "true" proton pump meaning that the protons which are pumped through CcO are not also substrates in the redox reactions which occur within this enzyme. Though a wealth of knowledge has been generated regarding CcO, much uncertainty remains about the microscopic details of the proton pumping process. Experimental methods have produced a detailed framework describing many aspects of CcO structure and function, however, probing this enzyme at the molecular level can be difficult. To this end, computational molecular modeling offers a complement to experimental efforts. The methods that are a part of computational molecular modeling can provide keen insight into biophysical processes. There are many different methods and ways to apply them, however, and it is not always straightforward how to best develop and deploy a model for a particular system. CcO presents an especially challenging system since the process of proton translocation involves levels of detail spanning electronic structure dynamics to large protein conformational changes. Computational methods must therefore be systematically tested and validated in order to increase confidence that their results are meaningful for investigations of CcO. In the current work, several computational models of CcO are compared. These models differ from one another in the level of detail describing a key region of the proton pumping pathway within CcO. This region contains a highly conserved residue, Glu-242 (bovine heart mitochondria numbering), which has been shown to be pivotal in relaying protons across the proton pumping pathway. The results of this work indicate that there are differences regarding the energetics and dynamics of Glu-242 side chain isomerization depending on the level of detail used in the model. These differences lead to differing descriptions of proton translocation as it involves Glu-242 and underscores the need to thoroughly examine the application of computational models. In Chapter 1, the major structures and functioning of CcO is outlined. The analogy that underlies this chapter is of CcO functioning similar to a macroscopic pump in moving protons from one side of the membrane to the other. The CcO reaction cycle is akin to the repetitive motions of a piston as it operates to pump material. In Chapter 2, the proton pump pathway through CcO is characterized. The focus then collects on a region of this pathway which is instrumental in the process of proton pumping named the "motif" region. Finally a four-state model is used to describe the participation in proton pumping of Glu-242 or its physiochemical analogue at this region. In Chapter 3, proton leaks and proton leak prevention are described. Proton leaks are thought to occur in some structural variants of CcO. In these cases, the unidirectional and productive movement of protons through CcO is compromised as indicated by abnormal proton pumping stoichiometry. Kinetic gating is a conceptual framework whereby the prevention of these leaks may be rationalized. This chapter ends with the description of a criterion that must be met in order to prevent protons from leaking. Chapter 4 introduces common methods used in molecular modeling. Finally, in Chapter 5 computational molecular models involving the motif region are compared. These models employ varying levels of detail. This offers a test of how increasing levels of model detail effects the conclusions which might be drawn regarding proton pumping. A proposal for how unidirectional proton translocation may occur in CcO is offered based on the results of the molecular models at the higher level of detail. In conclusion, these models are used to speculate on how proton leaks occur in structural variants of CcO and how unidirectional proton translocation may occur in CcO enzymes which lack Glu-242 or its equivalent. Part II: Ensemble Surrogate AutoShim: Probing Sensitivity to Parameter Modification (NIBR) Ensemble Surrogate AutoShim (ESA) is a powerful and versatile virtual docking and screening method which has proven to be useful in drug discovery and design. ESA is powerful in that it transforms general all-purpose scoring functions into target-tailored scoring functions using a combined 2D and 3D-QSAR based approach that involves virtual docking. These target-tailored scoring functions are then trained to reproduce bioactivity data against a given target resulting in a knowledge-based model that is used in virtual screening. Held-out test set validations of ESA models show that they routinely outperforms exclusively all-purpose scoring function based approaches. Chapter 1 outlines the ESA method in general. The versatility of the ESA method stems from the fact that various ligand preparation, docking and scoring, and pose filtering and refinement schemes may be implemented within the ESA framework. For example, the ESA method is open to the inclusion of any conventional all-purpose scoring function and docking program within its framework. This versatility offers flexibility in the implementation of the ESA method and invites an exploration of the parameters underlying this method. In Chapter 2, a systematic evaluation of ESA parameter modification is undertaken and quantified through statistical analysis. The results of this work indicate that several parameters significantly influence the quality of ESA models. Based on these results, a protocol is proposed which produces the most predictive ESA models on average of any parameter configuration and protocol studied so far on the data set evaluated.
Author: Holger Gohlke
Publisher: John Wiley & Sons
ISBN: 3527329668
Category : Medical
Languages : en
Pages : 361
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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: Karen Jayne Hand
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: Bing Wang
Publisher: Academic Press
ISBN: 0128244356
Category : Science
Languages : en
Pages : 280
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Book Description
Computational Intelligence in Protein-Ligand Interaction Analysis presents computational techniques for predicting protein-ligand interactions, recognizing protein interaction sites, and identifying protein drug targets. The book emphasizes novel approaches to protein-ligand interactions, including machine learning and deep learning, presenting a state-of-the-art suite of skills for researchers. The volume represents a resource for scientists, detailing the fundamentals of computational methods, showing how to use computational algorithms to study protein interaction data, and giving scientific explanations for biological data through computational intelligence. Fourteen chapters offer a comprehensive guide to protein interaction data and computational intelligence methods for protein-ligand interactions. Presents a guide to computational techniques for protein-ligand interaction analysis Guides researchers in developing advanced computational intelligence methods for the protein-ligand problem Identifies appropriate computational tools for various problems Demonstrates the use of advanced techniques such as vector machine, neural networks, and machine learning Offers the computational, mathematical and statistical skills researchers need
Author: Rajesh Sangar
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 4
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Book Description
Author: Barry L. Stoddard
Publisher: Humana
ISBN: 9781493935673
Category : Science
Languages : en
Pages : 0
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Book Description
This volume provides a collection of protocols and approaches for the creation of novel ligand binding proteins, compiled and described by many of today's leaders in the field of protein engineering. Chapters focus on modeling protein ligand binding sites, accurate modeling of protein-ligand conformational sampling, scoring of individual docked solutions, structure-based design program such as ROSETTA, protein engineering, and additional methodological approaches. Examples of applications include the design of metal-binding proteins and light-induced ligand binding proteins, the creation of binding proteins that also display catalytic activity, and the binding of larger peptide, protein, DNA and RNA ligands. 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.
Author: G. Ulrich Nienhaus
Publisher: Humana
ISBN: 9781617375255
Category : Science
Languages : en
Pages : 0
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Book Description
A readily reproducible collection of established and emerging techniques for studying the interaction between proteins and ligands, including biochemical/bulk techniques, structure analysis, spectroscopy, single-molecule studies, and theoretical/computational tools. Among the highlights are surface plasmon resonance (SPR) and reflectometric biosensor approaches, high-throughput screening with confocal optics microscopy, single molecule fluorescence and fluorescence correlation spectroscopy (FCS), atomic force microscopy (AFM), crystallography of reaction intermediates, and time-resolved x-ray crystallography. The protocols follow the successful Methods in Molecular BiologyTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.
Author: Robert M. Stroud
Publisher: Royal Society of Chemistry
ISBN: 0854043659
Category : Medical
Languages : en
Pages : 171
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Book Description
This insightful book represents the experience and understanding of the global experts in the field and spotlights both the structural and medicinal chemistry aspects of drug design. The need to 'encode' the physiological factors of pharmacology, a key area, is explored.
