Development Of Structure Based Computational Methods For Prediction And Design Of Protein Protein Interactions
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Development Of Structure Based Computational Methods For Prediction And Design Of Protein Protein Interactions
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Author : Brian Gregory Pierce
language : en
Publisher:
Release Date : 2008
Development Of Structure Based Computational Methods For Prediction And Design Of Protein Protein Interactions written by Brian Gregory Pierce and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.
Abstract: Protein-protein interactions play a key role in the functioning of cells and pathways, and understanding these interactions on a physical and structural level can help greatly in developing therapeutics for diseases. The large amount of protein structures available presents an immense opportunity to model and predict protein interactions using computational techniques. Here we describe the development of algorithms to predict protein complex structures (referred to as protein docking) and to design proteins to improve their interaction affinities. We also present experimental results validating our protein design approach. The protein docking work we present includes the symmetric multimer docking program M-ZDOCK as well as ZRANK which rescores docking predictions using a weighted potential. Both programs have been successful when applied to docking benchmarks and in the CAPRI experiment. In addition, we have used the M-ZDOCK program to produce a tetrameric model for a disease-associated protein, the latent nuclear antigen of the Kaposi's sarcoma-associated herpesvirus. We have also developed a protein design algorithm to improve the binding between two proteins, given their complex structure This was applied to a T cell receptor (TCR) to enhance its binding to the Major Histocompatibility Complex and peptide. Several of the point mutations predicted by our algorithm were verified experimentally to bind several times stronger than wild type; we then combined these mutations to produce a TCR with approximately 100-fold affinity improvement. Further testing of combinations of TCR point mutations has led to striking results regarding the kinetics and cooperativity of the mutations. Finally, we have used our protein design algorithm to predict designability of protein complexes from the Protein Data Bank, and identified the complex between CD4 and HIV gp120 as a target for future structure-based design efforts. Preliminary results for this project are given.
Protein Interactions Computational Methods Analysis And Applications
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Author : M Michael Gromiha
language : en
Publisher: World Scientific
Release Date : 2020-03-05
Protein Interactions Computational Methods Analysis And Applications written by M Michael Gromiha and has been published by World Scientific this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-03-05 with Science categories.
This book is indexed in Chemical Abstracts ServiceThe interactions of proteins with other molecules are important in many cellular activities. Investigations have been carried out to understand the recognition mechanism, identify the binding sites, analyze the the binding affinity of complexes, and study the influence of mutations on diseases. Protein interactions are also crucial in structure-based drug design.This book covers computational analysis of protein-protein, protein-nucleic acid and protein-ligand interactions and their applications. It provides up-to-date information and the latest developments from experts in the field, using illustrations to explain the key concepts and applications. This volume can serve as a single source on comparative studies of proteins interacting with proteins/DNAs/RNAs/carbohydrates and small molecules.
Computational Methods For Protein Structure Prediction And Modeling
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Author : Ying Xu
language : en
Publisher: Springer Science & Business Media
Release Date : 2010-05-05
Computational Methods For Protein Structure Prediction And Modeling written by Ying Xu and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-05-05 with Science categories.
Volume Two of this two-volume sequence presents a comprehensive overview of protein structure prediction methods and includes protein threading, De novo methods, applications to membrane proteins and protein complexes, structure-based drug design, as well as structure prediction as a systems problem. A series of appendices review the biological and chemical basics related to protein structure, computer science for structural informatics, and prerequisite mathematics and statistics.
Computational Methods For Protein Modeling And Design Based On An Ensemble View Of Protein Structures
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Author : Fan Zheng
language : en
Publisher:
Release Date : 2016
Computational Methods For Protein Modeling And Design Based On An Ensemble View Of Protein Structures written by Fan Zheng and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
Understanding sequence-structure relationships of proteins is a central theme of computational structural biology. To create accurate mapping between sequences and structures is a big computational challenge, because the inherent dynamics of protein molecules requires any structure to be seen as an ensemble containing a large number of structural states. In this thesis, I focus on developing new structural modeling methods representing two routes towards efficient sequence-structure mapping that are compatible with this ensemble view of structures. First, I will show that the relationships between the sequence and the structural ensemble of a protein can be revealed by breaking down the protein into constituent structural fragments, for which ensemble statistics can be obtained from the protein structure database. Second, sequence-structure relationships can be also extracted by combining explicit atomistic modeling of ensembles and statistical tools reducing the overall computational cost. Implications in structure prediction, mutational analysis, and design of protein-interaction modulators will be presented and discussed, showing the great promise held by these methods in further improving the state-of-the-art in a broad spectrum of applications in computational structural biology.
Computational Methods For Protein Structure Prediction And Modeling
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Author : Ying Xu
language : en
Publisher: Springer Science & Business Media
Release Date : 2007-08-24
Computational Methods For Protein Structure Prediction And Modeling written by Ying Xu and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007-08-24 with Science categories.
Volume One of this two-volume sequence focuses on the basic characterization of known protein structures, and structure prediction from protein sequence information. Eleven chapters survey of the field, covering key topics in modeling, force fields, classification, computational methods, and structure prediction. Each chapter is a self contained review covering definition of the problem and historical perspective; mathematical formulation; computational methods and algorithms; performance results; existing software; strengths, pitfalls, challenges, and future research.
Proteomics And Protein Protein Interactions
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Author : Gabriel Waksman
language : en
Publisher: Springer Science & Business Media
Release Date : 2005-12-21
Proteomics And Protein Protein Interactions written by Gabriel Waksman and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2005-12-21 with Medical categories.
The rapidly evolving field of protein science has now come to realize the ubiquity and importance of protein-protein interactions. It had been known for some time that proteins may interact with each other to form functional complexes, but it was thought to be the property of only a handful of key proteins. However, with the advent of high throughput proteomics to monitor protein-protein interactions at an organism level, we can now safely state that protein-protein interactions are the norm and not the exception. Thus, protein function must be understood in the larger context of the various binding complexes that each protein may form with interacting partners at a given time in the life cycle of a cell. Proteins are now seen as forming sophisticated interaction networks subject to remarkable regulation. The study of these interaction networks and regulatory mechanism, which I would like to term "systems proteomics," is one of the thriving fields of proteomics. The bird-eye view that systems proteomics offers should not however mask the fact that proteins are each characterized by a unique set of physical and chemical properties. In other words, no protein looks and behaves like another. This complicates enormously the design of high-throughput proteomics methods. Unlike genes, which, by and large, display similar physico-chemical behaviors and thus can be easily used in a high throughput mode, proteins are not easily amenable to the same treatment. It is thus important to remind researchers active in the proteomics field the fundamental basis of protein chemistry. This book attempts to bridge the two extreme ends of protein science: on one end, systems proteomics, which describes, at a system level, the intricate connection network that proteins form in a cell, and on the other end, protein chemistry and biophysics, which describe the molecular properties of individual proteins and the structural and thermodynamic basis of their interactions within the network. Bridging the two ends of the spectrum is bioinformatics and computational chemistry. Large data sets created by systems proteomics need to be mined for meaningful information, methods need to be designed and implemented to improve experimental designs, extract signal over noise, and reject artifacts, and predictive methods need to be worked out and put to the test. Computational chemistry faces similar challenges. The prediction of binding thermodynamics of protein-protein interaction is still in its infancy. Proteins are large objects, and simplifying assumptions and shortcuts still need to be applied to make simulations manageable, and this despite exponential progress in computer technology. Finally, the study of proteins impacts directly on human health. It is an obvious statement to say that, for decades, enzymes, receptors, and key regulator proteins have been targeted for drug discovery. However, a recent and exciting development is the exploitation of our knowledge of protein-protein interaction for the design of new pharmaceuticals. This presents particular challenges because protein-protein interfaces are generally shallow and interactions are weak. However, progress is clearly being made and the book seeks to provide examples of successes in this area.
Protein Protein Interactions And Networks
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Author : Anna Panchenko
language : en
Publisher: Springer Science & Business Media
Release Date : 2010-04-06
Protein Protein Interactions And Networks written by Anna Panchenko and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-04-06 with Science categories.
The biological interactions of living organisms, and protein-protein interactions in particular, are astonishingly diverse. This comprehensive book provides a broad, thorough and multidisciplinary coverage of its field. It integrates different approaches from bioinformatics, biochemistry, computational analysis and systems biology to offer the reader a comprehensive global view of the diverse data on protein-protein interactions and protein interaction networks.
Computational Methods For Protein Protein Complex Structure Prediction And Mass Spectrometry Based Identification
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Author : Weiwei Tong
language : en
Publisher:
Release Date : 2008
Computational Methods For Protein Protein Complex Structure Prediction And Mass Spectrometry Based Identification written by Weiwei Tong and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.
Abstract: Nearly all major processes in living cells are carried out by complex apparatus consisting of protein molecules. This thesis describes computational tools developed to help investigate two fundamental questions about proteins that underlie cell functions: how they interact with each other and form complex structures; and how they are expressed and modified in different cell states. In order to address the first question, several methods are developed to predict protein-protein complex structures. Protein interactions are energy driven processes. The prediction of protein complex structures is the search for the global minimum on the binding free-energy landscape. An approach is described that uses Van der Wools energy, desolvation energy and shape complementarity as the scoring functions and a five-dimensional fast Fourier transform algorithm to expedite the search. Two methods to screen and optimize the predicted protein complex structures are also introduced. They incorporate additional energy terms and clustering algorithms to provide more precise estimations of the binding free-energy. The same methods can also be used to predict hot spots, the mutations of which significantly alter the binding kinetics. To study the protein expression profiles, a two-step approach for protein identification using peptide mass fingerprinting data is developed. Peptide mass fingerprinting uses peptide masses determined by mass spectrometry to identify the peptides and subsequently, the proteins in the sample Peaks in the mass spectrum are associated with known peptide sequences in the database based on log-likelihood ratio test. A statistical algorithm is then used to identify proteins by comparing the probability of each protein's presence in the sample, given the peak assignments with the background probability. This method also discovers post-translational modifications in the identified proteins. The protein binding prediction program successfully predicts protein complex structures that closely resemble their native forms, as observed by x-ray crystallography or NMR. The refinements and hot spot predictions also give accurate and consistent results. The database search program that interprets mass spectrometry data is evaluated with artificial and experimental data. The program identifies proteins in the sample with high sensitivity and specificity. The results presented in this thesis demonstrate that computational methods help to better understand the structure and the composition of the protein machineries. All of the methods described herein have been implemented and made available for the research community over the Internet.
Computational Methods For Protein Structure Prediction And Modeling
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Author : Ying Xu
language : en
Publisher: Springer
Release Date : 2010-12-01
Computational Methods For Protein Structure Prediction And Modeling written by Ying Xu and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-12-01 with Science categories.
Volume Two of this two-volume sequence presents a comprehensive overview of protein structure prediction methods and includes protein threading, De novo methods, applications to membrane proteins and protein complexes, structure-based drug design, as well as structure prediction as a systems problem. A series of appendices review the biological and chemical basics related to protein structure, computer science for structural informatics, and prerequisite mathematics and statistics.
Computational Methods In Protein Evolution
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Author : Tobias Sikosek
language : en
Publisher:
Release Date : 2019
Computational Methods In Protein Evolution written by Tobias Sikosek and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with Protein engineering categories.