[PDF] Computational And Nmr Investigations Of Protein Structure eBook

Author : N. Rama Krishna
Publisher : Springer Science & Business Media
Page : 565 pages
File Size : 23,21 MB
Release : 2006-05-09
Category : Medical
ISBN : 0306470845

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Volume 17 is the second in a special topic series devoted to modern techniques in protein NMR, under the Biological Magnetic Resonance series. Volume 16, with the subtitle Modern Techniques in Protein NMR , is the first in this series. These two volumes present some of the recent, significant advances in the biomolecular NMR field with emphasis on developments during the last five years. We are honored to have brought together in these volume some of the world s foremost experts who have provided broad leadership in advancing this field. Volume 16 contains - vances in two broad categories: I. Large Proteins, Complexes, and Membrane Proteins and II. Pulse Methods. Volume 17 contains major advances in: I. Com- tational Methods and II. Structure and Dynamics. The opening chapter of volume 17 starts with a consideration of some important aspects of modeling from spectroscopic and diffraction data by Wilfred van Gunsteren and his colleagues. The next two chapters deal with combined automated assignments and protein structure determination, an area of intense research in many laboratories since the traditional manual methods are often inadequate or laborious in handling large volumes of NMR data on large proteins. First, Werner Braun and his associates describe their experience with the NOAH/DIAMOD protocol developed in their laboratory.

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Page : 0 pages
File Size : 33,52 MB
Release : 2015
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The theoretical and computational aspects of nuclear magnetic resonance (NMR) spectroscopy underlie the many diverse applications of NMR to studies of biomolecular dynamics, kinetics, and structure. The challenging aspects of biomolecular NMR spectroscopy can be divided into three major steps: (a) data acquisition and processing (development of methods for fast data collection and signal identification); (b) accurate mapping of spectral frequencies to atoms in the covalent structure of the molecule (as required for investigations of biomolecular dynamics and kinetics as well as structure calculation); (c) structure calculation and validation. I have investigated possibilities for improving current computational methods for each of these steps. In order to accelerate the process of NMR data acquisition, I have incorporated fast data collection methods into our probabilistic approach to simultaneous reduced-dimensionality data collection and assignment (discussed in Chapter 2). In order to simplify the process of assigning spectral frequencies derived from conventional triple-resonance NMR data to atoms of proteins, I designed a semi-automated method and trained an undergraduate student to implement it. In addition, because one of the important requirements of scientific research is the reproducibility of the study, I designed and developed a novel validation method called ARECA, for verifying the accuracy of chemical shift assignments (described in Chapter 3). A quote from one of the anonymous reviewers of our paper describing the method highlights its importance and practicality: "The new chemical shift validation method, ARECA, described in this work represents a fresh approach to a difficult problem, that has been an Achilles heel to protein NMR for more than three decades. ... I believe ARECA will become a very valuable addition to the 'must-use' tools of protein NMR spectroscopists." In order to facilitate applications of NMR for users with limited NMR expertise, I have introduced a framework (discussed in Chapter 4) for calculating three-dimensional structures of proteins from NMR data. This framework was designed to simplify the process while emphasizing the important role of validation in NMR studies

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Page : 0 pages
File Size : 26,93 MB
Release : 2013
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Three-dimensional structures of proteins determined in solution by NMR spectroscopy have the unique advantage of revealing details of molecular structure and dynamics in a physiologically relevant state; however, the many tedious steps needed to solve and validate a structure make this method challenging. The barriers to NMR structure determination become higher for larger proteins whose spectra are harder to resolve. It is clear that advances need to be made in automating protein structure determination by NMR spectroscopy. The goal of my research has been to use computational methods to advance the development of high-throughput NMR spectroscopy. Accelerating and streamlining the structure determination process will enable investigators to spend less time solving structures and more time investigating challenging biomolecular systems. My goals have been to develop an automation protocol that integrates multiple steps, ensures the robustness of each step, incorporates iterative corrections, and includes visualization tools to validate and extend the results. I developed PINE-SPARKY as a graphical interface for checking and extending automated assignments made by the PINE-NMR server. ADAPT-NMR directs fast data collection by reduced dimensionality on the basis of ongoing NMR assignments. I helped develop a version of ADAPT-NMR (originally only for Varian spectrometers) for Bruker spectrometers, and I created ADAPT-NMR Enhancer as a visualization tool for validating and extending assignments made by ADAPT-NMR on either spectrometer system. I developed the PONDEROSA package to automate the next steps. PONDEROSA carries out automatic picking of 3D-NOESY peaks and iterative structure determinations with the protein sequence and the assignments as inputs. These automation and visualization tools cover almost all of the steps involved in protein structure determination by NMR spectroscopy. As a practical test of this technology, I solved the structure of the 2A proteinase from the human rhinovirus. As a side project, I built a relational database (PACSY DB) that combines information from the Protein Data Bank (PDB) and the Biological Magnetic Resonance data Bank (BMRB) and incorporates tools for structure analysis. PACSY DB can carry out complex queries that combine atomic coordinates, NMR parameters, and structural features of proteins.

Author : Dmitry Shishmarev
Publisher :
Page : 428 pages
File Size : 17,57 MB
Release : 2014
Category : Nuclear magnetic resonance spectroscopy
ISBN :

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Nuclear magnetic resonance (NMR) spectroscopy is a powerful research technique widely used for establishing three-dimensional structures, dynamic properties and intermolecular interactions of proteins. Its non-destructiveness, high information content and applicability for a broad range of samples, both in solution and in the solid state, renders it one of the best tools in the modern structural biology. Liquid-state NMR spectroscopy, however, also has some drawbacks, such as relatively low inherent sensitivity, complexity of the resultant spectra, high time demands and poor suitability for the analysis of large biomolecular complexes and membrane proteins. Due to the variety of aspects that might be improved and optimised, it's been a target of constant development for the last few decades and still is a primary focus of modern biochemical science. The goal of my PhD projects was to understand and improve several aspects and techniques of liquid-state protein NMR spectroscopy, employing both computational and experimental analysis. In the present thesis, I describe the results of my work on a wide variety of topics. The first project is devoted to optimisations of experiments suffering from the radiation damping effect. The second project is a computational analysis aimed at investigations of the applicability of mobile lanthanide-binding tags in protein-ligand interaction studies. The third project is an investigation of the structure and functions of single-stranded DNA-binding protein (SSB) using solution NMR, targeted at the elucidation of the mechanism by which the protein plays its role in the metabolism of single-stranded DNA.

Author : Isabella C. Felli
Publisher : Springer
Page : 428 pages
File Size : 44,31 MB
Release : 2015-09-19
Category : Science
ISBN : 3319201646

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This book discusses the paradigm-shifting phenomenon of intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs). The properties of IDPs and IDPRs are highly complementary to those deriving from the presence of a unique and well-defined three-dimensional fold. Ignored for a long time in high-resolution studies of proteins, intrinsic protein disorder is now recognized as one of the key features for a large variety of cellular functions, where structural flexibility presents a functional advantage in terms of binding plasticity and promiscuity and this volume explores this exciting new research. Recent progress in the field has radically changed our perspective to study IDPs through NMR: increasingly complex IDPs can now be characterized, a wide range of observables can be determined reporting on the structural and dynamic properties, computational methods to describe the structure and dynamics are in continuous development and IDPs can be studied in environments as complex as whole cells. This volume communicates the new exciting possibilities offered by NMR and presents open questions to foster further developments. Intrinsically Disordered Proteins Studied by NMR Spectroscopy provides a snapshot to researchers entering the field as well as providing a current overview for more experienced scientists in related areas.