Development And Validation Of A Structure Based Computational Method For The Prediction Of Protein Specificity Profiles
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Development And Validation Of A Structure Based Computational Method For The Prediction Of Protein Specificity Profiles
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Author : Olivier Gagnon
language : en
Publisher:
Release Date : 2019
Development And Validation Of A Structure Based Computational Method For The Prediction Of Protein Specificity Profiles written by Olivier Gagnon and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.
Post-translational modification (PTM) of proteins by enzymes such as methyltransferases, kinases and deacetylases play a crucial role in the regulation of many metabolic pathways. Determining the substrate scope of these enzymes is essential when studying their biological role. However, the combinatorial nature of possible protein substrate sequences makes experimental screening assays intractable. To predict new substrates for proteins, various computational approaches have been developed. Our method relies on crystallographic data and a novel multistate computational protein design algorithm. We previously used our method to successfully predict four new substrates for SMYD2 (Lanouette S & Davey J.A., 2015), doubling the number of known targets for this PTM enzyme that has been difficult to characterize using other methods. This was possible by first extracting a specificity profile of Smyd2 using our algorithm and subsequently screening a peptide library for matching sequences. However, our method did not yield successful results when attempting to reproduce specificity profiles of other proteins (64% accuracy on average). Different protein environments have demonstrated limitations in the methodology and lead us to further develop the algorithm on a more thorough dataset. Using our new optimized method, specificity profile predictions increase by roughly 20% (84% accuracy on average), independent of the structural template used. The algorithm was then used to blindly predict a specificity profile for the methyltransferase Smyd3, an enzyme for which limited data is currently available. A library of 2550 peptides was screened with the predicted profile, yielding 123 matching sequences. We randomly chose 64 for experimental validation (SPOT peptide array) of methylation by Smyd3 and found 45 methylated and 19 non-methylated peptides (70% success rate). Finally, we released to the community a web version of the algorithm, which can be accessed as http://viper.science.uottawa.ca.
Progress And Challenges In Computational Structure Based Design And Development Of Biologic Drugs
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Author : Traian Sulea
language : en
Publisher: Frontiers Media SA
Release Date : 2024-03-25
Progress And Challenges In Computational Structure Based Design And Development Of Biologic Drugs written by Traian Sulea and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2024-03-25 with Science categories.
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.
Special Protein Molecules Computational Identification
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Author : Quan Zou
language : en
Publisher: MDPI
Release Date : 2018-08-09
Special Protein Molecules Computational Identification written by Quan Zou and has been published by MDPI this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-08-09 with Electronic books categories.
This book is a printed edition of the Special Issue "Special Protein Molecules Computational Identification" that was published in IJMS
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.
Comprehensive Medicinal Chemistry Iii
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Author :
language : en
Publisher: Elsevier
Release Date : 2017-06-03
Comprehensive Medicinal Chemistry Iii written by and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-06-03 with Technology & Engineering categories.
Comprehensive Medicinal Chemistry III, Eight Volume Set provides a contemporary and forward-looking critical analysis and summary of recent developments, emerging trends, and recently identified new areas where medicinal chemistry is having an impact. The discipline of medicinal chemistry continues to evolve as it adapts to new opportunities and strives to solve new challenges. These include drug targeting, biomolecular therapeutics, development of chemical biology tools, data collection and analysis, in silico models as predictors for biological properties, identification and validation of new targets, approaches to quantify target engagement, new methods for synthesis of drug candidates such as green chemistry, development of novel scaffolds for drug discovery, and the role of regulatory agencies in drug discovery. Reviews the strategies, technologies, principles, and applications of modern medicinal chemistry Provides a global and current perspective of today's drug discovery process and discusses the major therapeutic classes and targets Includes a unique collection of case studies and personal assays reviewing the discovery and development of key drugs
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.
Bioinformatics In Microbiota
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Author : Xing Chen
language : en
Publisher: Frontiers Media SA
Release Date : 2020-06-22
Bioinformatics In Microbiota written by Xing Chen and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-06-22 with categories.
Computational Intelligence And Predictive Analysis For Medical Science
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Author : Poonam Tanwar
language : en
Publisher: Walter de Gruyter GmbH & Co KG
Release Date : 2021-11-08
Computational Intelligence And Predictive Analysis For Medical Science written by Poonam Tanwar and has been published by Walter de Gruyter GmbH & Co KG this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-11-08 with Computers categories.
This book uncovers stakes and possibilities offered by Computational Intelligence and Predictive Analytics to Medical Science. The main focus is on data technologies,classification, analysis and mining, information retrieval, and in the algorithms needed to elaborate the informations. A section with use cases and applications follows the two main parts of the book, respectively dedicated to the foundations and techniques of the discipline.