From Protein Structure To Function With Bioinformatics

Proteins lie at the heart of almost all biological processes and have an incredibly wide range of activities. Central to the function of all proteins is their ability to adopt, stably or sometimes transiently, structures that allow for interaction with other molecules. An understanding of the structure of a protein can therefore lead us to a much improved picture of its molecular function. This realisation has been a prime motivation of recent Structural Genomics projects, involving large-scale experimental determination of protein structures, often those of proteins about which little is known of function. These initiatives have, in turn, stimulated the massive development of novel methods for prediction of protein function from structure. Since model structures may also take advantage of new function prediction algorithms, the first part of the book deals with the various ways in which protein structures may be predicted or inferred, including specific treatment of membrane and intrinsically disordered proteins. A detailed consideration of current structure-based function prediction methodologies forms the second part of this book, which concludes with two chapters, focusing specifically on case studies, designed to illustrate the real-world application of these methods. With bang up-to-date texts from world experts, and abundant links to publicly available resources, this book will be invaluable to anyone who studies proteins and the endlessly fascinating relationship between their structure and function.

This book discusses a broad range of basic and advanced topics in the field of protein structure, function, folding, flexibility, and dynamics. Starting with a basic introduction to protein purification, estimation, storage, and its effect on the protein structure, function, and dynamics, it also discusses various experimental and computational structure determination approaches; the importance of molecular interactions and water in protein stability, folding and dynamics; kinetic and thermodynamic parameters associated with protein-ligand binding; single molecule techniques and their applications in studying protein folding and aggregation; protein quality control; the role of amino acid sequence in protein aggregation; muscarinic acetylcholine receptors, antimuscarinic drugs, and their clinical significances. Further, the book explains the current understanding on the therapeutic importance of the enzyme dopamine beta hydroxylase; structural dynamics and motions in molecular motors; role of cathepsins in controlling degradation of extracellular matrix during disease states; and the important structure-function relationship of iron-binding proteins, ferritins. Overall, the book is an important guide and a comprehensive resource for understanding protein structure, function, dynamics, and interaction.

This book is about protein structural bioinformatics and how it can help understand and predict protein function. It covers structure-based methods that can assign and explain protein function based on overall folds, characteristics of protein surfaces, occurrence of small 3D motifs, protein-protein interactions and on dynamic properties. Such methods help extract maximum value from new experimental structures, but can often be applied to protein models. The book also, therefore, provides comprehensive coverage of methods for predicting or inferring protein structure, covering all structural classes from globular proteins and their membrane-resident counterparts to amyloid structures and intrinsically disordered proteins. The book is split into two broad sections, the first covering methods to generate or infer protein structure, the second dealing with structure-based function annotation. Each chapter is written by world experts in the field. The first section covers methods ranging from traditional homology modelling and fold recognition to fragment-based ab initio methods, and includes a chapter, new for the second edition, on structure prediction using evolutionary covariance. Membrane proteins and intrinsically disordered proteins are each assigned chapters, while two new chapters deal with amyloid structures and means to predict modes of protein-protein interaction. The second section includes chapters covering functional diversity within protein folds and means to assign function based on surface properties and recurring motifs. Further chapters cover the key roles of protein dynamics in protein function and use of automated servers for function inference. The book concludes with two chapters covering case studies of structure prediction, based respectively on crystal structures and protein models, providing numerous examples of real-world usage of the methods mentioned previously. This book is targeted at postgraduate students and academic researchers. It is most obviously of interest to protein bioinformaticians and structural biologists, but should also serve as a guide to biologists more broadly by highlighting the insights that structural bioinformatics can provide into proteins of their interest.

Structural Bioinformatics was the first major effort to showthe application of the principles and basic knowledge of the largerfield of bioinformatics to questions focusing on macromolecularstructure, such as the prediction of protein structure and howproteins carry out cellular functions, and how the application ofbioinformatics to these life science issues can improve healthcareby accelerating drug discovery and development. Designed primarilyas a reference, the first edition nevertheless saw widespread useas a textbook in graduate and undergraduate university coursesdealing with the theories and associated algorithms, resources, andtools used in the analysis, prediction, and theoreticalunderpinnings of DNA, RNA, and proteins. This new edition contains not only thorough updates of theadvances in structural bioinformatics since publication of thefirst edition, but also features eleven new chapters dealing withfrontier areas of high scientific impact, including: sampling andsearch techniques; use of mass spectrometry; genome functionalannotation; and much more. Offering detailed coverage for practitioners while remainingaccessible to the novice, Structural Bioinformatics, SecondEdition is a valuable resource and an excellent textbook for arange of readers in the bioinformatics and advanced biologyfields. Praise for the previous edition: "This book is a gold mine of fundamental and practicalinformation in an area not previously well represented in bookform." —Biochemistry and Molecular Education "... destined to become a classic reference work for workers atall levels in structural bioinformatics...recommended with greatenthusiasm for educators, researchers, and graduatestudents." —BAMBED "...a useful and timely summary of a rapidly expandingfield." —Nature Structural Biology "...a terrific job in this timely creation of a compilation ofarticles that appropriately addresses this issue." —Briefings in Bioinformatics

A look at the methods and algorithms used to predict proteinstructure A thorough knowledge of the function and structure of proteinsis critical for the advancement of biology and the life sciences aswell as the development of better drugs, higher-yield crops, andeven synthetic bio-fuels. To that end, this reference sheds lighton the methods used for protein structure prediction and revealsthe key applications of modeled structures. This indispensable bookcovers the applications of modeled protein structures and unravelsthe relationship between pure sequence information andthree-dimensional structure, which continues to be one of thegreatest challenges in molecular biology. With this resource, readers will find an all-encompassingexamination of the problems, methods, tools, servers, databases,and applications of protein structure prediction and they willacquire unique insight into the future applications of the modeledprotein structures. The book begins with a thorough introduction tothe protein structure prediction problem and is divided into fourthemes: a background on structure prediction, the prediction ofstructural elements, tertiary structure prediction, and functionalinsights. Within those four sections, the following topics arecovered: Databases and resources that are commonly used for proteinstructure prediction The structure prediction flagship assessment (CASP) and theprotein structure initiative (PSI) Definitions of recurring substructures and the computationalapproaches used for solving sequence problems Difficulties with contact map prediction and how sophisticatedmachine learning methods can solve those problems Structure prediction methods that rely on homology modeling,threading, and fragment assembly Hybrid methods that achieve high-resolution proteinstructures Parts of the protein structure that may be conserved and usedto interact with other biomolecules How the loop prediction problem can be used for refinement ofthe modeled structures The computational model that detects the differences betweenprotein structure and its modeled mutant Whether working in the field of bioinformatics or molecularbiology research or taking courses in protein modeling, readerswill find the content in this book invaluable.

One of the most pressing tasks in biotechnology today is to unlock the function of each of the thousands of new genes identified every day. Scientists do this by analyzing and interpreting proteins, which are considered the task force of a gene. This single source reference covers all aspects of proteins, explaining fundamentals, synthesizing the latest literature, and demonstrating the most important bioinformatics tools available today for protein analysis, interpretation and prediction. Students and researchers of biotechnology, bioinformatics, proteomics, protein engineering, biophysics, computational biology, molecular modeling, and drug design will find this a ready reference for staying current and productive in this fast evolving interdisciplinary field. Explains all aspects of proteins including sequence and structure analysis, prediction of protein structures, protein folding, protein stability, and protein interactions Presents a cohesive and accessible overview of the field, using illustrations to explain key concepts and detailed exercises for students.