Download or read book Computational Development Towards High throughput NMR based Protein Structure Determination written by and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Protein Structure written by Daniel Chasman and published by CRC Press. This book was released on 2003-03-18 with total page 534 pages. Available in PDF, EPUB and Kindle. Book excerpt: This text offers in-depth perspectives on every aspect of protein structure identification, assessment, characterization, and utilization, for a clear understanding of the diversity of protein shapes, variations in protein function, and structure-based drug design. The authors cover numerous high-throughput technologies as well as computational methods to study protein structures and residues. A valuable reference, this book reflects current trends in the effort to solve new structures arising from genome initiatives, details methods to detect and identify errors in the prediction of protein structural models, and outlines challenges in the conversion of routine processes into high-throughput platforms.
Download or read book Precise and Accurate Structural Genomics Protein Structure Determination Using RD and GFT NMR Spectroscopy written by and published by . This book was released on 2006 with total page 161 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nuclear magnetic resonance (NMR) has emerged as a powerful tool for determining three-dimensional structures of proteins in solution. The major part of this dissertation describes the efforts to deal with the core steps involved in NMR-base protein structure determination: NMR data collection, NMR data analysis, structure calculation and refinement. NMR data collection has been recognized as one of the major bottlenecks of NMR-base structure determination due to the necessarily long time. Chapter 2 and 3 describe two NMR data collection and analysis protocols for high-quality protein structure determination based on Reduced Dimensionality (RD) and G-matrix Fourier transform (GFT) NMR, respectively. The rapidly collected RD & GFT NMR data enabled high-quality structure determination of four structural genomics target proteins in high-throughput. Chapter 5 introduces the program UBNMR which was developed to facilitate NMR data analysis in general and RD & GFT NMR data pre-processing and data analysis in particular. RD and GFT NMR based protocols, with the aid of UBNMR, are expected to greatly impact on the NMR-based structural biology and structural genomics. In addition to rapid NMR data collection and analysis, structure calculation and refinement are also pivotal for obtaining the high-quality protein structures. Chapter 5 describes the analysis of the newly implemented simultaneous GFT NOESY to obtain an accurate and precise initial structural fold. Chapter 6 presents a protein structure refinement strategy using NOE data collected in supercooled water at low temperatures.
Download or read book Structure Computation and Dynamics in Protein NMR written by N. Rama Krishna and published by Springer Science & Business Media. This book was released on 2006-05-09 with total page 565 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Development and Application of Methodology for Rapid NMR Data Collection and Protein Structure Determination written by David Michael Parish and published by . This book was released on 2008 with total page 127 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis focuses on the development and application of methodology for rapid NMR data collection and protein structure determination. In chapter 1, simultaneously cycled (SC) NMR is introduced and exemplified by implementing without readout gradients a set of 2D [1 H, 1 H] SC Exclusive COSY (E. COSY) NMR experiments and with readout gradients a 2D [1 H, 1 H] double quantum filtered (DQF) COSY experiment. Spatially selective 1 H r.f. pulses are applied as composite pulses such that n steps of the respective cycles are effected simultaneously in n slices of the sample, thus reducing total acquisition time by a factor of n. In chapter 2, the structure of the 142-residue protein Q8ZP25_SALTY encoded in the genome of Salmonella typhimurium (NESG target StR70) was determined by NMR, refined using residual dipolar coupling constraints and compared to the X-ray structure of Q8ZP25_SALTY and the NMR structure of homologous protein HYAE_ECOLI. Protein Q8ZP25_SALTY belongs to Pfam PF07449, which itself belongs to the 'thioredoxin-like clan'. However, protein Q8ZP25_SALTY and the other proteins of Pfam PF07449, do not contain the Cys-X-X-Cys active site sequence motif of thioredoxin. The structures presented here exhibit the expected thioredoxin-like fold and support biochemical data suggesting that members of Pfam family PF07449 specifically interact with Tat signal peptides involved in hydrogenase assembly. In chapter 3, the development of a hardware and software infrastructure designed specifically to support high throughput NMR protein structure determination for structural genomics is described. In addition, a "consensus run" protocol is detailed which uses common results from two disparate programs for automated NMR structure determination, namely, CYANA and AUTOSTRUCTURE, to minimize errors in initial NOESY peak assignments. The high throughput infrastructure and consensus run have supported the determination of 47 protein structures to date. Finally, in chapter 4, the relaxation agent and gadolinium chelate gadoversetamide is used to affect the T 1 and T 2 relaxation times of amide and methyl protons in proteins in aqueous solution so as to map protein surfaces. The protocol is explored to distinguish surface and buried residues in order to identify homo-dimer interfaces.
Download or read book Computational Aspects of the Study of Biological Macromolecules by Nuclear Magnetic Resonance Spectroscopy written by Jeffrey C. Hoch and published by Springer. This book was released on 1991 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: Without computers - no modern NMR; Parametric estimation in 1-D, 2-D, and 3-D NMR; Computational aspects of multinuclear NMR spectroscopy of proteins at NMRFAM; Principles of multidimensional NMR techniques for measurement of J coupling constants; Comparison of the NMR and X-ray structures of hirudin; The application of the linear prediction principle to NMR spectroscopy; NMR data processing and structure calculations using parallel computers; Software approaches for determination of 3-dimensional molecular structures from multi-dimensional NMR; Applicability and limitations of three-dimensional NMR spectroscopy for the study of proteins in solution; The role of selective two-dimensional NMR correlation methods in supplementing computer-supported multiplet analysis by MARCO POLO; Application of maximum entropy methods to NMR spectra of proteins; Pattern recognition in two-dimensional NMR spectra of proteins; The application and development of software tools for the processinf and analysis of heteronuclear multi-dimensional NMR data; Distance geometry in torsion angle space: new developments and applications; Structure determination by NMR: the modeling of NMR parameters as ensemble averages; Time averaged distance restraints in NMR based structural refinement; Analysis of backbone dynamics of interleukin-1 beta; A new version of DADAS (Distance Analysis in Dihedral Angle Space) and its performance; An amateur looks at error analysis in the determination of protein structure by NMR; Structural interpretation of NMR data in the presence of motion; New interactive and automatic algorithms for the assignment of NMR spectra; Outline of a computer program for the analysis of protein NMR spectra; Assignment of the NMR spectra of homologous proteins; Incorporation of internal motion in NMR refinements based on NOESY data; Refinement of three-dimensional protein and DNA structures in solution from NMR data; How to deal with spin-diffusion and internal mobility in biomolecules: a relaxation matrix approach; Interactive computer graphics in the assignment of protein 2D and 3D NMR spectra; Determination of large protein structures from NMR data: definition of the solution structure of the TRP repressor; Interpretation of NMR data in terms of protein structure: summary of a round table discussion; Fast calculation of the relaxation matrix; NMR structures of proteins using stereospecific assignments and relaxation matrix refinement in a hybrid method of distance geometry and simulated annealing; A critique of the interpretation of nuclear Overhauser effects of duplex DNA; Improvement in resolution with nonlinear methods applied to NMR signals from macromolecules; STELLA and CLAIRE: a seraglio of programs for human-aided assignment of 2D 1H NMR spectra of proteins; MolSkop: towards NMR molecular scope; Ribonuclease H: full assignment of backbone proton resonances with heteronuclear 3D NMR and solution structure; Sampling properties of simulated annealing and distance geometry.
Download or read book Structural Genomics and High Throughput Structural Biology written by Michael Sundstrom and published by CRC Press. This book was released on 2005-08-23 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: Researchers in structural genomics continue to search for biochemical and cellular functions of proteins as well as the ways in which proteins assemble into functional pathways and networks using either experimental or computational approaches. Based on the experience of leading international experts, Structural Genomics and High Throughput Stru
Download or read book Biological NMR Spectroscopy written by John L. Markley and published by Oxford University Press. This book was released on 1997-01-30 with total page 375 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents a critical assessment of progress on the use of nuclear magnetic resonance spectroscopy to determine the structure of proteins, including brief reviews of the history of the field along with coverage of current clinical and in vivo applications. The book, in honor of Oleg Jardetsky, one of the pioneers of the field, is edited by two of the most highly respected investigators using NMR, and features contributions by most of the leading workers in the field. It will be valued as a landmark publication that presents the state-of-the-art perspectives regarding one of today's most important technologies.
Download or read book Protein Structure Determination by Paramagnetic NMR and Computational Hybrid Approach written by Kala Bharath Pilla and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational modelling of proteins that rely on either de novo or evolutionary based approaches often produce poor quality structures, primarily due to the limitations in their algorithms or forcefields. Traditional experimental techniques such as X-ray crystallography depend on narrow set of crystallographic conditions while solution/solid state nuclear magnetic resonance (NMR) spectroscopy relies on cumbersome spectral analysis and complete resonance assignments. These traditional approaches are slow and costly endeavours. Computational/experimental hybrid approaches on the other hand provide a new avenue for reliable, rapid and cost-effective structure determination. Paramagnetic NMR offers easy generation of useful and sparse structural information which can be implemented as restraints in structure prediction algorithms. Pseudocontact shifts (PCS) are the most powerful of structural restraints generated by paramagnetic NMR which are long range in nature and can be easily obtained by simple 2D NMR experiments. This thesis demonstrates different approaches involved in protein structure calculations using PCS restraints in Rosetta. Chapter 2 demonstrates structure determination using PCS restraints exclusively obtained from protein samples in microcrystalline state by magic angle spinning (MAS) NMR spectroscopy. Chapter 3 discusses the implementation of using PCS data from multiple metal centres to precisely determine the location of spins in space in a manner analogues to GPS-satellites. Chapter 4 extends the usage of PCS data from multiple metal centres to capture distinct conformational states in proteins. Chapter 5 demonstrates new techniques especially developed for structure determination of large proteins involving super secondary structure motifs (Smotifs) and data driven iterative resampling. These different computational techniques serve the goal of determining accurate 3D models using minimal experimental data, which are applicable to proteins systems that are currently beyond the realm of traditional experimental approaches.
Download or read book Computing and Information Sciences written by J. C. Misra and published by Alpha Science Int'l Ltd.. This book was released on 2003 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: Introduces educational units with various trends in Computing and Information Sciences. This title offers information on different topics such as: Evoultion of Processor Architecture; Hybrid Systems; Support Vector Machines; Paritioning Techniques for Reconfigurable Computing; and more.
Download or read book Computational Systems Bioinformatics written by Peter Markstein and published by World Scientific. This book was released on 2008 with total page 355 pages. Available in PDF, EPUB and Kindle. Book excerpt: This proceedings volume contains 29 papers covering many of the latest developments in the fast-growing field of bioinformatics. The contributions span a wide range of topics, including computational genomics and genetics, protein function and computational proteomics, the transcriptome, structural bioinformatics, microarray data analysis, motif identification, biological pathways and systems, and biomedical applications. The papers not only cover theoretical aspects of bioinformatics but also delve into the application of new methods, with input from computation, engineering and biology disciplines. This multidisciplinary approach to bioinformatics gives these proceedings a unique viewpoint of the field.
Download or read book Phytochemistry Computational Tools and Databases in Drug Discovery written by Chukwuebuka Egbuna and published by Elsevier. This book was released on 2022-11-30 with total page 494 pages. Available in PDF, EPUB and Kindle. Book excerpt: Phytochemistry, Computational Tools and Databases in Drug Discovery presents the state-of-the-art in computational methods and techniques for drug discovery studies from medicinal plants. Various tools and databases for virtual screening and characterization of plant bioactive compounds and their subsequent predictions on biological targets for the discovery of new drugs against specific diseases are presented, along with computational tools for the prediction of the toxic effects of phytochemicals on living systems. The book also provides in-depth insight on the applications of these computational tools as well as the databases that describe the interactions of phytochemicals with diseases along with predictions for druggable bioactive compounds. Useful for drug developers, medicinal chemists, toxicologists, phytochemists, plant biochemists and analytical chemists, this book clearly presents the various computational techniques, tools and databases for phytochemical research. Provides the various databases, methods and procedures for computational drug discovery in plants Includes insights into the predictors for properties of phytochemicals against different diseases Discusses the applications of computational tools and their databases
Download or read book New Computational Methods for 3D NMR Data Analysis and Protein Structure Determination in High dimensional Internal Coordinate Space written by Garry Paul Gippert and published by . This book was released on 1995 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: New computational methods were developed for the determination of primary chemical shift assignments and measurement of three-bond scalar J-coupling constants using multi-dimensional NMR data; and high-dimensional, systematic search for poly-peptide conformations subject to distance geometry constraints. Two methods were developed for conformational search in a space consisting of variable torsion angles. Method I performs a recursive search for linear chains. Method II performs a binary tree search for linear or branched systems. Trial conformations are rejected based on distance and scalar coupling bounds violations, including novel bounds on distance ratios, coupling ratios, and a 'degenerate' treatment of equivalent and prochiral atoms. A hierarchical arrangement of sub-searches is used to prune the high-dimensional space. The binary search (Method II) employs Unix 'pipes' and may be distributed over a computer network in a multi-processor environment, and may additionally utilize bounds on relative orientations of chain segments. 1H, 13C and 15N chemical shift assignments were obtained for recombinant poplar plastocyanin (rPc) from homonuclear and heteronuclear 2D and 3D NMR spectra. A semi-automated reduction of 3D NH-based spectra into a series of interleaved 1D vectors facilitated the sequential assignment process. Sidechain assignments were completed by the prediction and interactive, visual correction of crosspeak locations based on expected scalar and through-space connectivities. A similar procedure was used to identify correct beta-strand alignment based on total integrated NOE volume. Secondary proton chemical shifts were compared for five homologous plastocyanins. Distinct chemical shift variations were correlated with changes in primary sequence and led to a critical analysis of structural differences observed within the protein family. Scalar J-coupling constants between backbone HN and H-alpha protons of rPc were measured in three different NMR spectra--by lineshape analysis for 1H COSY and 3D HNCA-J crosspeaks, and curve fitting to modulated 1H, 15N-HSQC crosspeak intensities. Solution measurements of J(HN,H-alpha) were compared to values predicted from the high-resolution X-ray crystal structure using the Karplus relationship. Notable deviations occur for residues that are involved in intermolecular backbone contacts in the crystal, or are likely to be due to conformational averaging in solution, and includes a subset of residues in the copper-binding loop.
Download or read book DOE Genomics written by and published by . This book was released on 2005 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Distance based NMR Structure Determination and Refinement written by Feng Cui and published by . This book was released on 2005 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein structures play a pivotal role in understanding protein functions. X-ray crystallography and nuclear magnetic resonance spectroscopy (NMR) are two main experimental approaches for protein structure determination. The structures determined by NMR are not as accurate as those by X-ray crystallography in general, due to limited distance data (e.g. NOEs) that can be generated from NMR experiments. The NMR modeling algorithms are not well developed either, to produce high-quality structures with desired accuracy and efficiency. To address the NMR modeling issues, a so-called geometric build-up approach for NMR modeling has been developed, which remarkably reduces computing time in determining NMR structures. On the other hand, a novel bioinformatics approach aimed at increasing the accuracy of the NMR-determined structures has been proposed and tested, by deriving more distance constraints, in addition to the experimental ones, from the databases of known protein structures. Results show that with database-derived distance constraints, NMR-determined structures can be improved significantly based on various standard evaluations such as acceptance rate, RMSD to corresponding X-ray structures, Ramachandran plot, etc. The derived constraints are also able to enhance and even replace some experimental restraints such as short-range NOEs and dihedral angles, holding a promise of reducing experimental and labor costs. In addition, they can be applied to improving the structure of the under-determined regions of proteins such as the loop regions of the prion protein, a protein responsible to a group of important neurodegenerative diseases including the Mad Cow Disease.
Download or read book Algorithms in Structural Molecular Biology written by Bruce R. Donald and published by MIT Press. This book was released on 2023-08-15 with total page 497 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book High Performance Computational Solutions in Protein Bioinformatics written by Dariusz Mrozek and published by Springer. This book was released on 2014-06-04 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent developments in computer science enable algorithms previously perceived as too time-consuming to now be efficiently used for applications in bioinformatics and life sciences. This work focuses on proteins and their structures, protein structure similarity searching at main representation levels and various techniques that can be used to accelerate similarity searches. Divided into four parts, the first part provides a formal model of 3D protein structures for functional genomics, comparative bioinformatics and molecular modeling. The second part focuses on the use of multithreading for efficient approximate searching on protein secondary structures. The third and fourth parts concentrate on finding 3D protein structure similarities with the support of GPUs and cloud computing. Parts three and four both describe the acceleration of different methods. The text will be of interest to researchers and software developers working in the field of structural bioinformatics and biomedical databases.
