Computer simulation has become the main engine of development in statistical mechanics. In structural biology, computer simulation constitutes the main theoretical tool for structure determination of proteins and for calculation of the free energy of binding, which are important in drug design. Entropy and Free Energy in Structural Biology leads the reader to the simulation technology in a systematic way. The book, which is structured as a course, consists of four parts: Part I is a short course on probability theory emphasizing (1) the distinction between the notions of experimental probability, probability space, and the experimental probability on a computer, and (2) elaborating on the mathematical structure of product spaces. These concepts are essential for solving probability problems and devising simulation methods, in particular for calculating the entropy. Part II starts with a short review of classical thermodynamics from which a non-traditional derivation of statistical mechanics is devised. Theoretical aspects of statistical mechanics are reviewed extensively. Part III covers several topics in non-equilibrium thermodynamics and statistical mechanics close to equilibrium, such as Onsager relations, the two Fick's laws, and the Langevin and master equations. The Monte Carlo and molecular dynamics procedures are discussed as well. Part IV presents advanced simulation methods for polymers and protein systems, including techniques for conformational search and for calculating the potential of mean force and the chemical potential. Thermodynamic integration, methods for calculating the absolute entropy, and methodologies for calculating the absolute free energy of binding are evaluated. Enhanced by a number of solved problems and examples, this volume will be a valuable resource to advanced undergraduate and graduate students in chemistry, chemical engineering, biochemistry biophysics, pharmacology, and computational biology.

Fundamentals of Molecular Structural Biology reviews the mathematical and physical foundations of molecular structural biology. Based on these fundamental concepts, it then describes molecular structure and explains basic genetic mechanisms. Given the increasingly interdisciplinary nature of research, early career researchers and those shifting into an adjacent field often require a "fundamentals" book to get them up-to-speed on the foundations of a particular field. This book fills that niche. - Provides a current and easily digestible resource on molecular structural biology, discussing both foundations and the latest advances - Addresses critical issues surrounding macromolecular structures, such as structure-based drug discovery, single-particle analysis, computational molecular biology/molecular dynamic simulation, cell signaling and immune response, macromolecular assemblies, and systems biology - Presents discussions that ultimately lead the reader toward a more detailed understanding of the basis and origin of disease

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

The definitive guide to mass spectrometry techniques in biology and biophysics The use of mass spectrometry (MS) to study the architecture and dynamics of proteins is increasingly common within the biophysical community, and Mass Spectrometry in Structural Biology and Biophysics: Architecture, Dynamics, and Interaction of Biomolecules, Second Edition provides readers with detailed, systematic coverage of the current state of the art. Offering an unrivalled overview of modern MS-based armamentarium that can be used to solve the most challenging problems in biophysics, structural biology, and biopharmaceuticals, the book is a practical guide to understanding the role of MS techniques in biophysical research. Designed to meet the needs of both academic and industrial researchers, it makes mass spectrometry accessible to professionals in a range of fields, including biopharmaceuticals. This new edition has been significantly expanded and updated to include the most recent experimental methodologies and techniques, MS applications in biophysics and structural biology, methods for studying higher order structure and dynamics of proteins, an examination of other biopolymers and synthetic polymers, such as nucleic acids and oligosaccharides, and much more. Featuring high-quality illustrations that illuminate the concepts described in the text, as well as extensive references that enable the reader to pursue further study, Mass Spectrometry in Structural Biology and Biophysics is an indispensable resource for researchers and graduate students working in biophysics, structural biology, protein chemistry, and related fields.

Advances in Protein and Peptide Sciences is a book series focused on leading-edge research on the structure, physical properties, and functions of proteins and peptides. The series presents highly cited contributions first published in the journal Current Protein and Peptide Science. Authors of these contributions have updated their work with new experimental data and references following their initial research. Each volume highlights a number of important topics in current research in the field of protein and peptide chemistry and molecular biology, including membrane proteins and their interactions with ligands, computational methods, and proteins in disease and biotechnology.

While the field of computational structural biology or structural bioinformatics is rapidly developing, there are few books with a relatively complete coverage of such diverse research subjects studied in the field as X-ray crystallography computing, NMR structure determination, potential energy minimization, dynamics simulation, and knowledge-based modeling. This book helps fill the gap by providing such a survey on all the related subjects. Comprising a collection of lecture notes for a computational structural biology course for the Program on Bioinformatics and Computational Biology at Iowa State University, the book is in essence a comprehensive summary of computational structural biology based on the author's own extensive research experience, and a review of the subject from the perspective of a computer scientist or applied mathematician. Readers will gain a deeper appreciation of the biological importance and mathematical novelty of the research in the field.

Understand the latest experimental tools in structural biology with this pioneering work Structural biology seeks to understand the chemical mechanisms and functions of biological molecules, such as proteins, based on their atomic structures. Until recently, these structures have been studied only statically, using procedures which deliberately freeze atomic motion. However, freezing eliminates the rapid structural motions so essential to biological activity and function; the molecules are inactive. But with the recent development of X-ray free electron laser (XFEL) sources, efforts to conduct dynamic experiments have expanded using the principles of dynamics and kinetics to capture active biological molecules as they function. Dynamics and Kinetics in Structural Biology promotes the development of these experiments and their successful application. It grounds readers in the foundational principles of dynamics and kinetics; proceeds through extended discussions of experimental procedures, data analysis techniques; and explores experimental frontiers in structural dynamics. The book will aid researchers to gather and interpret cutting-edge data on the dynamic structure of biological molecules, under conditions where they retain their biological functions. Dynamics and Kinetics in Structural Biology offers readers: Authorship by founding figures in the field In-depth presentation of time-resolved X-ray crystallography, solution scattering, and more A pioneering contribution to a rapidly developing field of study Dynamics and Kinetics in Structural Biology is essential reading for graduate students, scientists, researchers and industry professionals engaged in structural studies of biological systems. Industry professionals considering dynamic studies in the development of new product lines will also benefit.

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

An overview of algorithms important to computational structural biology that addresses such topics as NMR and design and analysis of proteins.Using the tools of information technology to understand the molecular machinery of the cell offers both challenges and opportunities to computational scientists. Over the past decade, novel algorithms have been developed both for analyzing biological data and for synthetic biology problems such as protein engineering. This book explains the algorithmic foundations and computational approaches underlying areas of structural biology including NMR (nuclear magnetic resonance); X-ray crystallography; and the design and analysis of proteins, peptides, and small molecules. Each chapter offers a concise overview of important concepts, focusing on a key topic in the field. Four chapters offer a short course in algorithmic and computational issues related to NMR structural biology, giving the reader a useful toolkit with which to approach the fascinating yet thorny computational problems in this area. A recurrent theme is understanding the interplay between biophysical experiments and computational algorithms. The text emphasizes the mathematical foundations of structural biology while maintaining a balance between algorithms and a nuanced understanding of experimental data. Three emerging areas, particularly fertile ground for research students, are highlighted: NMR methodology, design of proteins and other molecules, and the modeling of protein flexibility. The next generation of computational structural biologists will need training in geometric algorithms, provably good approximation algorithms, scientific computation, and an array of techniques for handling noise and uncertainty in combinatorial geometry and computational biophysics. This book is an essential guide for young scientists on their way to research success in this exciting field.

This book constitutes the refereed proceedings of the 11th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2007, held in Oakland, CA, USA in April 2007. The 37 revised full papers address all current issues in algorithmic, theoretical, and experimental bioinformatics.