On Protein Structure Function And Modularity From An Evolutionary Perspective

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On Protein Structure Function And Modularity From An Evolutionary Perspective
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Author : Robert Pilstål
language : en
Publisher: Linköping University Electronic Press
Release Date : 2018-05-23
On Protein Structure Function And Modularity From An Evolutionary Perspective written by Robert Pilstål and has been published by Linköping University Electronic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-05-23 with categories.
We are compounded entities, given life by a complex molecular machinery. When studying these molecules we have to make sense of a diverse set of dynamical nanostructures with wast and intricate patterns of interactions. Protein polymers is one of the major groups of building blocks of such nanostructures which fold up into more or less distinct three dimensional structures. Due to their shape, dynamics and chemical properties proteins are able to perform a plethora of specific functions essential to all known cellular lifeforms. The connection between protein sequence, translated into protein structure and in the continuation into protein function is well accepted but poorly understood. Malfunction in the process of protein folding is known to be implicated in natural aging, cancer and degenerative diseases such as Alzheimer's. Protein folds are described hierarchically by structural ontologies such as SCOP, CATH and Pfam all which has yet to succeed in deciphering the natural language of protein function. These paradigmatic views centered on protein structure fail to describe more mutable entities, such as intrinsically disordered proteins (IDPs) which lack a clear defined structure. As of 2012, about two thirds of cancer patients was predicted to survive past 5 years of diagnosis. Despite this, about a third do not survive and numerous of successfully treated patients suffer from secondary conditions due to chemotherapy, surgery and the like. In order to handle cancer more efficiently we have to better understand the underlying molecular mechanisms. Elusive to standard methods of investigation, IDPs have a central role in pathology; dysfunction in IDPs are key factors in cellular system failures such as cancer, as many IDPs are hub regulators for major cell functions. These IDPs carry short conserved functional boxes, that are not described by known ontologies, which suggests the existence of a smaller entity. In an investigation of a pair of such boxes of c-MYC, a plausible structural model of its interacting with Pin1 emerged, but such a model still leaves the observer with a puzzle of understanding the actual function of that interaction. If the protein is represented as a graph and modeled as the interaction patterns instead of as a structural entity, another picture emerges. As a graph, there is a parable from that of the boxes of IDPs, to that of sectors of allosterically connected residues and the theory of foldons and folding units. Such a description is also useful in deciphering the implications of specific mutations. In order to render a functional description feasible for both structured and disordered proteins, there is a need of a model separate from form and structure. Realized as protein primes, patterns of interaction, which has a specific function that can be defined as prime interactions and context. With function defined as interactions, it might be possible that the discussion of proteins and their mechanisms is thereby simplified to the point rendering protein structural determination merely supplementary to understanding protein function. Människan byggs upp av celler, de i sin tur består av än mindre beståndsdelar; livets molekyler. Dessa fungerar som mekaniska byggstenar, likt maskiner och robotar som sliter vid fabrikens band; envar utförandes en absolut nödvändig funktion för cellens, och hela kroppens, fortsatta överlevnad. De av livets molekyler som beskrivs centralt i den här avhandling är proteiner, vilka i sin tur består utav en lång kedja, med olika typer av länkar, som likt garn lindar upp sig i ett nystan av en (mer eller mindre...) bestämd struktur som avgör dess roll och funktion i cellen. Intrinsiellt oordnade proteiner (IDP) går emot denna enkla åskådning; de är proteiner som saknar struktur och beter sig mer likt spaghetti i vatten än en maskin. IDP är ändå funktionella och bär på centrala roller i cellens maskineri; exempel är oncoproteinet c-Myc som agerar "gaspedal" för cellen - fel i c-Myc's funktion leder till att cellerna löper amok, delar sig hejdlöst och vi får cancer. Man har upptäckt att c-Myc har en ombytlig struktur vi inte kan se; studier av punktvisa förändringar, mutationer, i kedjan av byggstenar hos c-Myc visar att många länkar har viktiga roller i funktionen. Detta ger oss bättre förståelse om cancer men samtidigt är laboratoriearbetet både komplicerat och dyrt; här kan evolutionen vägleda oss och avslöja hemligheterna snabbare. Molekylär evolution studeras genom att beräkna variation i proteinkedjan mellan besläktade arter som finns lagrade i databaser; detta visar snabbt, via nätverksanalys och grafteori, vilka delar av proteinet som är centrala och kopplade till varandra av nödvändighet för artens fortlevnad. På så vis hjälper evolutionen oss att förstå proteinfunktioner via modeller baserade på proteinernas interaktioner snarare än deras struktur. Samma modeller kan nyttjas för att förstå dynamiska förlopp och skillnader mellan normala och patologiska varianter av proteiner; mutationer kan uppstå i vår arvsmassa som kan leda till sjukdom. Genom analys av proteinernas kopplingsnätverk i grafmodellerna kan man bättre förutsäga vilka mutationer som är farligare än andra. Dessutom har det visat sig att en sådan representation kan ge bättre förståelse för den normala funktionen hos ett protein än vad en proteinstruktur kan. Här introduceras även konceptet proteinprimärer, vilket är en abstrakt representation av proteiner centrerad på deras interaktiva mönster, snarare än på partikulär form och struktur. Det är en förhoppning att en sådan representation skall förenkla diskussionen anbelangande proteinfunktion så till den grad att strukturbestämmelse av proteiner, som är en mycket kostsam och tidskrävande process, till viss mån kan anses vara sekundär i betydelse jämfört med funktionellt modellerande baserat på evolutionära data extraherade ur våra sekvensdatabaser.
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Author : Taylor & Francis Group
language : en
Publisher: Garland Science
Release Date : 2010-12-31
written by Taylor & Francis Group and has been published by Garland Science this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-12-31 with categories.
Molecular Biology Of The Cell
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Author :
language : en
Publisher:
Release Date : 2004
Molecular Biology Of The Cell written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004 with Cells categories.
Insights In Systems Biology Research
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Author : Gary An
language : en
Publisher: Frontiers Media SA
Release Date : 2025-06-10
Insights In Systems Biology Research written by Gary An 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 2025-06-10 with Science categories.
Summary of Topic: This collection represents an interdisciplinary exploration of systems biology and systems medicine, integrating advanced methodologies from computational modeling, deep neural networks, and multiomics to improve understanding and treatment of human diseases and biological mechanisms. Emphasis is placed on cutting-edge technologies, including deep learning for statistical inference from gene expression data and noncoding genetic variants, quantitative systems pharmacology for virtual patient generation, and semi-mechanistic modeling applied to novel therapies such as CAR T-cell interventions. The articles further highlight disease modeling across various scales, exemplified through multi-scale simulation frameworks applied to complex conditions such as COVID-19 long-term sequelae, rheumatoid arthritis, epilepsy, and tuberculosis. Additionally, the importance of modularity in biological networks, developments in functional annotation of microbial transporters, and new approaches towards bioengineered bacterial consortia through molecular communication are discussed. This collection informs us of the ongoing efforts to harness computational power and biological insights to advance personalized medicine, improve therapeutic strategies, and deepen our understanding of complex biological phenomena. ----- Systems Biology has undergone significant transformations due to the pioneering efforts of researchers worldwide. The discipline now spans several subfields, such as Neuroscience, Genetics and Genomics, Medicine, among others, each advancing the field in unique ways through innovative technologies and insightful discoveries. This evolution is celebrated in a curated collection by Frontiers in Systems Biology, which aims to highlight the state-of-the-art developments and set the stage for future inquiries and applications in the field. This collection actively showcases the overlap of technology with theoretical advancements, creating a broad framework from which new methodologies and strategies are born. This Research Topic aims to provide an overview of the most recent progress in Systems Biology. It seeks to outline the impacts that the integration of disparate biological research areas can have in solving complex biological problems and advancing human health. Without losing sight of the past achievements, the goal is to explore the potential of future advancements, addressing the challenges that remain at the forefront of this vibrant field. The scope of this Research Topic is broadly defined yet focused on areas where significant innovative strides have been made. We welcome contributions that emphasize: - Integrative approaches in Systems Neuroscience - Contemporary breakthroughs in Genetics and Genomics - The use of Multiscale Mechanistic Modelling to represent biological interfaces - Bridging gaps between experimental and computational biology in Translational Systems Biology - Enhancing methodologies in Data and Model Integration This collection welcomes contributions from Editorial Board Members or those referred by a board member, reflecting on current developments and plotting pathways for upcoming research endeavors. Authors are encouraged to engage critically with their fields, identifying current challenges and proposing novel solutions to advance the understanding of complex systems within biology.
Artificial Life Vi
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Author : Christoph Adami
language : en
Publisher: MIT Press
Release Date : 1998
Artificial Life Vi written by Christoph Adami and has been published by MIT Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1998 with Computers categories.
Since their inception in 1987, the Artificial Life meetings have grown from small workshops to truly international conferences, reflecting the fields increasing appeal to researchers in all areas of science.
Bioinformatics
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Author : Dev Bukhsh Singh
language : en
Publisher: Academic Press
Release Date : 2021-10-21
Bioinformatics written by Dev Bukhsh Singh and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-10-21 with Medical categories.
Bioinformatics: Methods and Applications provides a thorough and detailed description of principles, methods, and applications of bioinformatics in different areas of life sciences. It presents a compendium of many important topics of current advanced research and basic principles/approaches easily applicable to diverse research settings. The content encompasses topics such as biological databases, sequence analysis, genome assembly, RNA sequence data analysis, drug design, and structural and functional analysis of proteins. In addition, it discusses computational approaches for vaccine design, systems biology and big data analysis, and machine learning in bioinformatics.It is a valuable source for bioinformaticians, computer biologists, and members of biomedical field who needs to learn bioinformatics approaches to apply to their research and lab activities. - Covers basic and more advanced developments of bioinformatics with a diverse and interdisciplinary approach to fulfill the needs of readers from different backgrounds - Explains in a practical way how to decode complex biological problems using computational approaches and resources - Brings case studies, real-world examples and several protocols to guide the readers with a problem-solving approach
Modular Evolution
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Author : Lucio Vinicius
language : en
Publisher: Cambridge University Press
Release Date : 2010-07-15
Modular Evolution written by Lucio Vinicius and has been published by Cambridge University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-07-15 with Social Science categories.
Natural selection is more than the survival of the fittest: it is a force engendering higher biological complexity. Presenting a new explanation for the tendency of life to become more complex through evolution, this book offers an introduction to the key debates in evolutionary theory, including the role of genes and sex in evolution, the adaptive reasons for senescence and death and the origin of neural information. The author argues that biological complexity increased through the process of 'modularity transfer': modular phenotypes (proteins, somatic cells, learned behaviours) evolved into new modular information carriers (regulatory proteins, neural cells, words), giving rise to new information systems and higher levels of biological organisation. Modular Evolution makes sense of the unique place of humans in evolution, both as the pinnacle of biological complexity and inventors of non-biological evolution.
Applied Dairy Microbiology Second Edition
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Author : Elmer H. Marth
language : en
Publisher: CRC Press
Release Date : 2001-05-22
Applied Dairy Microbiology Second Edition written by Elmer H. Marth and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001-05-22 with Technology & Engineering categories.
This thoroughly revised and updated reference provides comprehensive coverage of the latest developments and scientific advances in dairy microbiology—emphasizing probiotics, fermented dairy products, disease prevention, and public health and regulatory control standards for dairy foods. Containing more than 2350 bibliographic citations, tables, drawings and photographs—550 more than the previous edition—Applied Dairy Microbiology, Second Edition is an invaluable reference for all food and dairy microbiologists, scientists, and technologists; toxicologists; food processors; sanitarians; dietitians; epidemiologists; bacteriologists; public health and regulatory personnel; and veterinarians; and an important text for upper-level undergraduate, graduate, and continuing-education students in these disciplines. ·
Biomass Biofuels Biochemicals
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Author : Ram Sarup Singh
language : en
Publisher: Elsevier
Release Date : 2019-01-31
Biomass Biofuels Biochemicals written by Ram Sarup Singh and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-01-31 with Technology & Engineering categories.
Biomass, Biofuels and Biochemicals: Advances in Enzyme Technology provides state-of-the-art information on the fundamental aspects and current perspectives in enzyme technology to graduate students, postgraduates and researchers working in industry and academia. The book provides information about the use of enzyme technology as an important tool for biotechnological processes, including food, feed, fuels, textiles, paper, energy and environmental applications. The search for improvements in existing enzyme-catalyzed processes dictates the need to update information on various enzyme technologies. The book gives a snapshot of current practice and research in the area of enzyme technology. - Includes current and emerging technologies for the development of novel enzyme catalysis - Outlines immobilized enzymes and their implications - Refers to enzymes as diagnostic tools - Includes metabolic engineering principles for improving industrial enzymes
Annual Reports In Computational Chemistry
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Author : Ralph A. Wheeler
language : en
Publisher: Elsevier
Release Date : 2008-10-30
Annual Reports In Computational Chemistry written by Ralph A. Wheeler and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-10-30 with Science categories.
Annual Reports in Computational Chemistry is a new periodical providing timely and critical reviews of important topics in computational chemistry as applied to all chemical disciplines. Topics covered include quantum chemistry, molecular mechanics, force fields, chemical education, and applications in academic and industrial settings. Each volume is organized into (thematic) sections with contributions written by experts. Focusing on the most recent literature and advances in the field, each article covers a specific topic of importance to computational chemists. Annual Reports in Computational Chemistry is a "must" for researchers and students wishing to stay up-to-date on current developments in computational chemistry.* Broad coverage of computational chemistry and up-to-date information * Topics covered include bioinformatics, drug discovery, protein NMR, simulation methodologies, and applications in academic and industrial settings * Each chapter reviews the most recent literature on a specific topic of interest to computational chemists