Computational Methods For Macromolecules

This special volume collects invited articles by participants of the Third International Workshop on Methods for Macromolecular Modeling, Courant Institute of Mathematical Sciences, Oct. 12-14, 2000. Leading developers of methods for biomolecular simulations review advances in Monte Carlo and molecular dynamics methods, free energy computational methods, fast electrostatics (particle-mesh Ewald and fast multipole methods), mathematics, and molecular neurobiology, nucleic acid simulations, enzyme reactions, and other essential applications in biomolecular simulations. A Perspectives article by the editors assesses the directions and impact of macromolecular modeling research, including genomics and proteomics. These reviews and original papers by applied mathematicians, theoretical chemists, biomedical researchers, and physicists are of interest to interdisciplinary research students, developers and users of biomolecular methods in academia and industry.

This book provides a comprehensive overview of modern computer-based techniques for analyzing the structure, properties and dynamics of biomolecules and biomolecular processes. It is organized in four main parts; the first one deals with methodology of molecular simulations; the second one with applications of molecular simulations; the third one introduces bioinformatics methods and the use of experimental information in molecular simulations; the last part reports on selected applications of molecular quantum mechanics. This second edition has been thoroughly revised and updated to include the latest progresses made in the respective field of research.

Thereexistawiderangeofapplicationswhereasigni?cantfractionofthe- mentum and energy present in a physical problem is carried by the transport of particles. Depending on the speci?capplication, the particles involved may be photons, neutrons, neutrinos, or charged particles. Regardless of which phenomena is being described, at the heart of each application is the fact that a Boltzmann like transport equation has to be solved. The complexity, and hence expense, involved in solving the transport problem can be understood by realizing that the general solution to the 3D Boltzmann transport equation is in fact really seven dimensional: 3 spatial coordinates, 2 angles, 1 time, and 1 for speed or energy. Low-order appro- mations to the transport equation are frequently used due in part to physical justi?cation but many in cases, simply because a solution to the full tra- port problem is too computationally expensive. An example is the di?usion equation, which e?ectively drops the two angles in phase space by assuming that a linear representation in angle is adequate. Another approximation is the grey approximation, which drops the energy variable by averaging over it. If the grey approximation is applied to the di?usion equation, the expense of solving what amounts to the simplest possible description of transport is roughly equal to the cost of implicit computational ?uid dynamics. It is clear therefore, that for those application areas needing some form of transport, fast, accurate and robust transport algorithms can lead to an increase in overall code performance and a decrease in time to solution.

Progressively builds a deep understanding of macromolecular behavior Based on each of the authors' roughly forty years of biophysics research and teaching experience, this text instills readers with a deep understanding of the biophysics of macromolecules. It sets a solid foundation in the basics by beginning with core physical concepts such as thermodynamics, quantum chemical models, molecular structure and interactions, and water and the hydrophobic effect. Next, the book examines statistical mechanics, protein-ligand binding, and conformational stability. Finally, the authors address kinetics and equilibria, exploring underlying theory, protein folding, and stochastic models. With its strong emphasis on molecular interactions, Equilibria and Kinetics of Biological Macromolecules offers new insights and perspectives on proteins and other macromolecules. The text features coverage of: Basic theory, applications, and new research findings Related topics in thermodynamics, quantum mechanics, statistical mechanics, and molecular simulations Principles and applications of molecular simulations in a dedicated chapter and interspersed throughout the text Macromolecular binding equilibria from the perspective of statistical mechanics Stochastic processes related to macromolecules Suggested readings at the end of each chapter include original research papers, reviews and monographs, enabling readers to explore individual topics in greater depth. At the end of the text, ten appendices offer refreshers on mathematical treatments, including probability, computational methods, Poisson equations, and defining molecular boundaries. With its classroom-tested pedagogical approach, Equilibria and Kinetics of Biological Macromolecules is recommended as a graduate-level textbook for biophysics courses and as a reference for researchers who want to strengthen their understanding of macromolecular behavior.

Approaches to the recovery of three-dimensional information on a biological object, which are often formulated or implemented initially in an intuitive way, are concisely described here based on physical models of the object and the image-formation process. Both three-dimensional electron microscopy and X-ray tomography can be captured in the same mathematical framework, leading to closely-related computational approaches, but the methodologies differ in detail and hence pose different challenges. The editors of this volume, Gabor T. Herman and Joachim Frank, are experts in the respective methodologies and present research at the forefront of biological imaging and structural biology. Computational Methods for Three-Dimensional Microscopy Reconstruction will serve as a useful resource for scholars interested in the development of computational methods for structural biology and cell biology, particularly in the area of 3D imaging and modeling.

Molecular biology and genetics are fast-growing fields with significant results and findings being reported virtually every day. Raw data from the wet lab accumulate at an astonishing rate, making it necessary to analyze the biological data with the use of computers. This book reveals how the current challenges of molecular biology and genetics are met with computer and mathematical treatments. A combined effort of the Computational Genetics and Biophysics Group (Supercomputer Computations Research Institute, USA), the Theoretical Molecular Genetics (Russian Academy of Sciences, Russia) and the Bioinformatics Group (Consiglio Nazionale delle Ricerche, Italy), many of these findings are firsthand discoveries made by these groups. The book emphasizes the fundamental principles of the structural-functional organization of the 3 major classes of genetic macromolecules: DNA, RNA and proteins. It also introduces universally applicable theoretical principles into the enormous realm of raw data and develops an integrative, theoretical computer approach to the analysis of these macromolecules to gain insights into the complexities of their function and evolution.

This volume is the scientific chronicle of the NATO Advanced Research Workshop on Computational Aspects of the Study of Biological Macro molecules by Nuclear Magnetic Resonance Spectroscopy, which was held June 3-8, 1990 at Il Ciocco, near Barga, Italy. The use of computers in the study of biological macromolecules by NMR spectroscopy is ubiquitous. The applications are diverse, including data col lection, reduction, and analysis. Furthermore, their use is rapidly evolv ing, driven by the development of new experimental methods in NMR and molecular biology and by phenomenal increases in computational perfor mance available at reasonable cost. Computers no longer merely facilitate, but are now absolutely essential in the study of biological macromolecules by NMR, due to the size and complexity of the data sets that are obtained from modern experiments. The Workshop, and this proceedings volume, provide a snapshot of the uses of computers in the NMR of biomolecules. While by no means exhaustive, the picture that emerges illustrates both the· importance and the diversity of their application.

In the decade since the publication of the first edition of "Crystallographic Methods and Protocols", the field has seen several major developments that have both accelerated the pace of structure determination and made crystallography accessible to a broader range of investigators. "Volume I, Preparation and Crystallization of Macromolecules" is dedicated to the crystallization and ways to increase the odds of obtaining crystals in macromolecules, while "Volume 2, Structure Determination" covers both computational methods for characterizing crystals and solving structures.