Advance In Structural Bioinformatics

Structural Bioinformatics was the first major effort to show the application of the principles and basic knowledge of the larger field of bioinformatics to questions focusing on macromolecular structure, such as the prediction of protein structure and how proteins carry out cellular functions, and how the application of bioinformatics to these life science issues can improve healthcare by accelerating drug discovery and development. Designed primarily as a reference, the first edition nevertheless saw widespread use as a textbook in graduate and undergraduate university courses dealing with the theories and associated algorithms, resources, and tools used in the analysis, prediction, and theoretical underpinnings of DNA, RNA, and proteins. This new edition contains not only thorough updates of the advances in structural bioinformatics since publication of the first edition, but also features eleven new chapters dealing with frontier areas of high scientific impact, including: sampling and search techniques; use of mass spectrometry; genome functional annotation; and much more. Offering detailed coverage for practitioners while remaining accessible to the novice, Structural Bioinformatics, Second Edition is a valuable resource and an excellent textbook for a range of readers in the bioinformatics and advanced biology fields. Praise for the previous edition: "This book is a gold mine of fundamental and practical information in an area not previously well represented in book form." —Biochemistry and Molecular Education "... destined to become a classic reference work for workers at all levels in structural bioinformatics...recommended with great enthusiasm for educators, researchers, and graduate students." —BAMBED "...a useful and timely summary of a rapidly expanding field." —Nature Structural Biology "...a terrific job in this timely creation of a compilation of articles that appropriately addresses this issue." —Briefings in Bioinformatics

This text examines in detail mathematical and physical modeling, computational methods and systems for obtaining and analyzing biological structures, using pioneering research cases as examples. As such, it emphasizes programming and problem-solving skills. It provides information on structure bioinformatics at various levels, with individual chapters covering introductory to advanced aspects, from fundamental methods and guidelines on acquiring and analyzing genomics and proteomics sequences, the structures of protein, DNA and RNA, to the basics of physical simulations and methods for conformation searches. This book will be of immense value to researchers and students in the fields of bioinformatics, computational biology and chemistry. Dr. Dongqing Wei is a Professor at the Department of Bioinformatics and Biostatistics, College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, China. His research interest is in the general area of structural bioinformatics.

The Beauty of Protein Structures and the Mathematics behind Structural Bioinformatics Providing the framework for a one-semester undergraduate course, Structural Bioinformatics: An Algorithmic Approach shows how to apply key algorithms to solve problems related to macromolecular structure. Helps Students Go Further in Their Study of Structural Biology Following some introductory material in the first few chapters, the text solves the longest common subsequence problem using dynamic programming and explains the science models for the Nussinov and MFOLD algorithms. It then reviews sequence alignment, along with the basic mathematical calculations needed for measuring the geometric properties of macromolecules. After looking at how coordinate transformations facilitate the translation and rotation of molecules in a 3D space, the author introduces structural comparison techniques, superposition algorithms, and algorithms that compare relationships within a protein. The final chapter explores how regression and classification are becoming more useful in protein analysis and drug design. At the Crossroads of Biology, Mathematics, and Computer Science Connecting biology, mathematics, and computer science, this practical text presents various bioinformatics topics and problems within a scientific methodology that emphasizes nature (the source of empirical observations), science (the mathematical modeling of the natural process), and computation (the science of calculating predictions and mathematical objects based on mathematical models).

Advances in Protein Molecular and Structural Biology Methods offers a complete overview of the latest tools and methods applicable to the study of proteins at the molecular and structural level. The book begins with sections exploring tools to optimize recombinant protein expression and biophysical techniques such as fluorescence spectroscopy, NMR, mass spectrometry, cryo-electron microscopy, and X-ray crystallography. It then moves towards computational approaches, considering structural bioinformatics, molecular dynamics simulations, and deep machine learning technologies. The book also covers methods applied to intrinsically disordered proteins (IDPs)followed by chapters on protein interaction networks, protein function, and protein design and engineering. It provides researchers with an extensive toolkit of methods and techniques to draw from when conducting their own experimental work, taking them from foundational concepts to practical application. Presents a thorough overview of the latest and emerging methods and technologies for protein study Explores biophysical techniques, including nuclear magnetic resonance, X-ray crystallography, and cryo-electron microscopy Includes computational and machine learning methods Features a section dedicated to tools and techniques specific to studying intrinsically disordered proteins

This book reviews the advances and challenges of structure-based drug design in the preclinical drug discovery process, addressing various diseases, including malaria, tuberculosis and cancer. Written by internationally recognized researchers, this edited book discusses how the application of the various in-silico techniques, such as molecular docking, virtual screening, pharmacophore modeling, molecular dynamics simulations, and residue interaction networks offers insights into pharmacologically active novel molecular entities. It presents a clear concept of the molecular mechanism of different drug targets and explores methods to help understand drug resistance. In addition, it includes chapters dedicated to natural-product- derived medicines, combinatorial drug discovery, the CryoEM technique for structure-based drug design and big data in drug discovery. The book offers an invaluable resource for graduate and postgraduate students, as well as for researchers in academic and industrial laboratories working in the areas of chemoinformatics, medicinal and pharmaceutical chemistry and pharmacoinformatics.

This book is the first one specifically dedicated to the structural bioinformatics of membrane proteins. With a focus on membrane proteins from the perspective of bioinformatics, the present work covers a broad spectrum of topics in evolution, structure, function, and bioinformatics of membrane proteins focusing on the most recent experimental results. Leaders in the field who have recently reported breakthrough advances cover algorithms, databases and their applications to the subject. The increasing number of recently solved membrane protein structures makes the expert coverage presented here very timely. Structural bioinformatics of membrane proteins has been an active area of research over the last thee decades and proves to be a growing field of interest.

The first mention of the word protein was from a letter sent by Jöns Jakob Berzelius to Gerhardus Johannes Mulder on 10. July 1838, where he wrote: The name protein that I propose for the organic oxide of fibrin and albumin, I wanted to derive from p??te???, [protas meaning of primary importance ] because it appears to be the primitive or principal substance of animal nutrition. A protein is a complex, high-molecular-mass, organic compound that consists of amino acids joined by peptide bonds. Proteins are essential to the structure and function of all living cells and viruses. Different proteins perform a wide variety of biological functions. Some proteins are enzymes, which catalyze chemical reactions. Other proteins play structural or mechanical roles, such as those that form the struts and joints of the cytoskeleton, which is like a system of scaffolding within a cell. Still more functions filled by proteins include immune response and the storage and transport of various ligands. Proteins fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native state, which is determined by its sequence of amino acids. Thus, proteins are their own polymers, with amino acids being the monomers. We can refer to four distinct aspects of a protein's structure: (i) Primary structure: the amino acid sequence, (ii) Secondary structure: highly patterned sub-structures, (iii) Tertiary structure: the overall shape of a single protein molecule, (iv) Quaternary structure: the shape or structure that results from the interaction of more than one protein molecule, usually called protein subunits in this context, which function as part of the larger assembly or protein complex. The knowledge of protein structures can help in numerous cases, e.g. to annotate unknown function, to understand the function mechanism and so their dysfunctions, to design drugs, to propose new evolutionary prospects... In 1951, Pauling and Corey performed seven studies published back-to-back, all on the subject of protein structure, presenting the alpha-helix and the beta-sheet described the polypeptide backbone folding stabilized by hydrogen bonds [1, 2]. In 1958, myoglobin was the first protein structure solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew. This work was acknowledged by a Nobel Prize in Chemistry [3, 4]. Since, the number of available protein structures has grown slowly, and increase greatly this last decade. Despite this progress, the gap between the number of sequences and structures known at the atomic scale is still considerable (3,170,612 protein sequences in UniProt database vs. 39,678 structures in Protein DataBank in August 2006). NMR or X-ray experiments even if being the most appropriate methods to gain such information are in fact strongly limited because of the different unavoidable steps, to be performed initially. Indeed before putting the sample in the experimental devices, one needs to express to extract, and to purify the protein while maintaining its functional properties. This last point is of course the most important one. Such necessity is as much difficult to obey for membrane proteins that frequently denature when extract from their material environment. Not denature approaches are required that could provide details of protein structures. Structural bioinformatics approaches belong to this field. In this book, many researchers present their work on structural bioinformatics and / or structural genomics. The first parts of the book focus on the analysis and prediction of protein structures with classical and innovative approaches (Chapters 1 to 6). The second part of this book focus on new approaches to analyze protein functions using protein structures (Chapters 7 to 11), while last part describe some pertinent examples of globular and transmembrane proteins (Chapters 12 to 16). Benros, Martin et al. present the different aspects of secondary structure assignment and describe the resulting problems (Chapter 1). The following chapter by Tyagi et al. extends this reviewing to novel other approaches, named the structural alphabets, composed of sets or libraries of local structure proteins (Chapter 2). Fuchs et al. present an up-to-date review about the assignment, analysis and prediction of well-characterized local protein structure, the b-turns (Chapter 3). Kondratova and Efimov present the effect of structural context on specificity of polar interactions in proteins, highlighting that differently packed a-helices had distinct interhelical networks of hydrogen and salt bonds (Chapter 4). Roterman et al. present a review about their innovative recent researches on early-stage protein folding using an ellipsoid model (Chapter 5). Carpentier et al. present a review the structural similarity detection and especially at a large scale within a database (Chapter 6). Reuter reviews the different know approaches dedicated to Normal Mode Analyses and the corresponding existing databases and web services (Chapter 7). Baaden and Lavery in their review highlight the constraints imposed by the size, time and energy scales of biomolecules depending on the range and details of the performed simulations (Chapter 8). Autin, Montes et al. reviews an impressive number of docking tools dedicated to protein-protein docking and virtual ligand screening methods highlighting the problem and challenges of this research area (Chapter 9). Bastard and Prévost focus their review on the difficult case of flexible macromolecular docking (Chapter 10). Loch reviews structure-based virtual screening process detailing the various in silico methods used (Chapter 11). Gowri et al. present the application and challenges of comparative modeling applied at the genomic scale (Chapter 12). Krupa and Srinivasan develop an analysis about the evolution of FAD synthetases and associated functional domains (Chapter 13), while Bhaduri and John focus on the particular case of the Protein O-Phosphatase families (Chapter 14). Transmembrane structures are available in very few numbers, thus Simoes et al. show the different aspect of homology modeling in the case of Kca3.1 calcium activated K+ channel and of Ca2+ selective voltage insensitive TRPV5 channel (Chapter 15). Debret and Etchebest review the evolution of the researches and views of a particular mecanosensitive transmembrane protein, the MscL (Chapter 16). This book is dedicated to the memory of Pr. Serge Hazout. He was an excellent scientist who had worked on numerous subjects such as human genetics [5], image pattern [6], sequence alignments [7], protein docking [8], protein side chain prediction [9], and recently developed numerous new approaches dedicated to structural alphabets [10-13] and microarray data analysis [14], but more important, he was greatly human. Chapter 17 present so a review and new developments on a difficult problem: How compare the predictions of more than 2 states? Pr. Serge Hazout presents different known and new statistical criteria to assess the performance of prediction approaches.

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.