From Protein Sequence to Motion to Function PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download From Protein Sequence to Motion to Function PDF full book. Access full book title From Protein Sequence to Motion to Function by Adam Damry. Download full books in PDF and EPUB format.
Author: Adam Damry
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Protein dynamics are critical to the structure and function of proteins. However, due to the complexity they inherently bring to the protein design problem, dynamics historically have not been considered in computational protein design (CPD). Herein, we present meta-MSD, a new CPD methodology for the design of protein dynamics. We applied our methodology to the design of a novel mode of conformational exchange in Streptococcal protein G domain B1, producing dynamic variants we termed DANCERs. Predictions were validated by NMR characterization of selected DANCERs, confirming that our meta-MSD framework is suitable for the computational design of protein dynamics. We then performed a thorough NMR characterization of the sequence determinants of dynamics in one DANCER, isolating two mutations responsible for the novel dynamics this protein exhibits. The first, A34F, is responsible for destabilizing the highly stable native G?1 conformation, allowing the protein to sample other conformational states. The second, V39L mediates subtle interactions that stabilize the designed conformational trajectory in the context of the A34F mutation. Together, these results highlight the role of protein plasticity in the development of dynamics and the need for highly accurate computational tools to approach similar design problems. Finally, we present an NMR-based characterization of structural dynamics in a family of related red fluorescent proteins (RFPs) and pinpoint regions of the RFP structure where dynamics correlate to RFP brightness. This overview of the RFP dynamics-function relationship will be used in future projects to perform a computation design of functional dynamics in RFPs.
Author: Adam Damry
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Protein dynamics are critical to the structure and function of proteins. However, due to the complexity they inherently bring to the protein design problem, dynamics historically have not been considered in computational protein design (CPD). Herein, we present meta-MSD, a new CPD methodology for the design of protein dynamics. We applied our methodology to the design of a novel mode of conformational exchange in Streptococcal protein G domain B1, producing dynamic variants we termed DANCERs. Predictions were validated by NMR characterization of selected DANCERs, confirming that our meta-MSD framework is suitable for the computational design of protein dynamics. We then performed a thorough NMR characterization of the sequence determinants of dynamics in one DANCER, isolating two mutations responsible for the novel dynamics this protein exhibits. The first, A34F, is responsible for destabilizing the highly stable native G?1 conformation, allowing the protein to sample other conformational states. The second, V39L mediates subtle interactions that stabilize the designed conformational trajectory in the context of the A34F mutation. Together, these results highlight the role of protein plasticity in the development of dynamics and the need for highly accurate computational tools to approach similar design problems. Finally, we present an NMR-based characterization of structural dynamics in a family of related red fluorescent proteins (RFPs) and pinpoint regions of the RFP structure where dynamics correlate to RFP brightness. This overview of the RFP dynamics-function relationship will be used in future projects to perform a computation design of functional dynamics in RFPs.
Author: Amit Kessel
Publisher: CRC Press
ISBN: 1498747183
Category : Computers
Languages : en
Pages : 985
Get Book Here
Book Description
Introduction to Proteins provides a comprehensive and state-of-the-art introduction to the structure, function, and motion of proteins for students, faculty, and researchers at all levels. The book covers proteins and enzymes across a wide range of contexts and applications, including medical disorders, drugs, toxins, chemical warfare, and animal behavior. Each chapter includes a Summary, Exercises, and References. New features in the thoroughly-updated second edition include: A brand-new chapter on enzymatic catalysis, describing enzyme biochemistry, classification, kinetics, thermodynamics, mechanisms, and applications in medicine and other industries. These are accompanied by multiple animations of biochemical reactions and mechanisms, accessible via embedded QR codes (which can be viewed by smartphones) An in-depth discussion of G-protein-coupled receptors (GPCRs) A wider-scale description of biochemical and biophysical methods for studying proteins, including fully accessible internet-based resources, such as databases and algorithms Animations of protein dynamics and conformational changes, accessible via embedded QR codes Additional features Extensive discussion of the energetics of protein folding, stability and interactions A comprehensive view of membrane proteins, with emphasis on structure-function relationship Coverage of intrinsically unstructured proteins, providing a complete, realistic view of the proteome and its underlying functions Exploration of industrial applications of protein engineering and rational drug design Each chapter includes a Summary, Exercies, and References Approximately 300 color images Downloadable solutions manual available at www.crcpress.com For more information, including all presentations, tables, animations, and exercises, as well as a complete teaching course on proteins' structure and function, please visit the author's website. Praise for the first edition "This book captures, in a very accessible way, a growing body of literature on the structure, function and motion of proteins. This is a superb publication that would be very useful to undergraduates, graduate students, postdoctoral researchers, and instructors involved in structural biology or biophysics courses or in research on protein structure-function relationships." --David Sheehan, ChemBioChem, 2011 "Introduction to Proteins is an excellent, state-of-the-art choice for students, faculty, or researchers needing a monograph on protein structure. This is an immensely informative, thoroughly researched, up-to-date text, with broad coverage and remarkable depth. Introduction to Proteins would provide an excellent basis for an upper-level or graduate course on protein structure, and a valuable addition to the libraries of professionals interested in this centrally important field." --Eric Martz, Biochemistry and Molecular Biology Education, 2012
Author:
Publisher:
ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0
Get Book Here
Book Description
Author: Amit Kessel
Publisher: CRC Press
ISBN: 1439810729
Category : Medical
Languages : en
Pages : 623
Get Book Here
Book Description
As the tools and techniques of structural biophysics assume greater roles in biological research and a range of application areas, learning how proteins behave becomes crucial to understanding their connection to the most basic and important aspects of life. With more than 350 color images throughout, Introduction to Proteins: Structure, Function, and Motion presents a unified, in-depth treatment of the relationship between the structure, dynamics, and function of proteins. Taking a structural–biophysical approach, the authors discuss the molecular interactions and thermodynamic changes that transpire in these highly complex molecules. The text incorporates various biochemical, physical, functional, and medical aspects. It covers different levels of protein structure, current methods for structure determination, energetics of protein structure, protein folding and folded state dynamics, and the functions of intrinsically unstructured proteins. The authors also clarify the structure–function relationship of proteins by presenting the principles of protein action in the form of guidelines. This comprehensive, color book uses numerous proteins as examples to illustrate the topics and principles and to show how proteins can be analyzed in multiple ways. It refers to many everyday applications of proteins and enzymes in medical disorders, drugs, toxins, chemical warfare, and animal behavior. Downloadable questions for each chapter are available at CRC Press Online.
Author: Gregory A. Petsko
Publisher: New Science Press
ISBN: 0878936637
Category : Proteins
Languages : en
Pages : 220
Get Book Here
Book Description
Each title in the 'Primers in Biology' series is constructed on a modular principle that is intended to make them easy to teach from, to learn from, and to use for reference.
Author: Ivet Bahar
Publisher: Garland Science
ISBN: 1351815016
Category : Science
Languages : en
Pages : 337
Get Book Here
Book Description
Protein Actions: Principles and Modeling is aimed at graduates, advanced undergraduates, and any professional who seeks an introduction to the biological, chemical, and physical properties of proteins. Broadly accessible to biophysicists and biochemists, it will be particularly useful to student and professional structural biologists and molecular biophysicists, bioinformaticians and computational biologists, biological chemists (particularly drug designers) and molecular bioengineers. The book begins by introducing the basic principles of protein structure and function. Some readers will be familiar with aspects of this, but the authors build up a more quantitative approach than their competitors. Emphasizing concepts and theory rather than experimental techniques, the book shows how proteins can be analyzed using the disciplines of elementary statistical mechanics, energetics, and kinetics. These chapters illuminate how proteins attain biologically active states and the properties of those states. The book ends with a synopsis the roles of computational biology and bioinformatics in protein science.
Author: Guang Song
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Protein folding is considered to be one of the grand challenge problems in biology. Protein folding refers to how a protein's amino acid sequence, under certain physiological conditions, folds into a stable close-packed three-dimensional structure known as the native state. There are two major problems in protein folding. One, usually called protein structure prediction, is to predict the structure of the protein's native state given only the amino acid sequence. Another important and strongly related problem, often called protein folding, is to study how the amino acid sequence dynamically transitions from an unstructured state to the native state. In this dissertation, we concentrate on the second problem. There are several approaches that have been applied to the protein folding problem, including molecular dynamics, Monte Carlo methods, statistical mechanical models, and lattice models. However, most of these approaches suffer from either overly-detailed simulations, requiring impractical computation times, or overly-simplified models, resulting in unrealistic solutions. In this work, we present a novel motion planning based framework for studying protein folding. We describe how it can be used to approximately map a protein's energy landscape, and then discuss how to find approximate folding pathways and kinetics on this approximate energy landscape. In particular, our technique can produce potential energy landscapes, free energy landscapes, and many folding pathways all from a single roadmap. The roadmap can be computed in a few hours on a desktop PC using a coarse potential energy function. In addition, our motion planning based approach is the first simulation method that enables the study of protein folding kinetics at a level of detail that is appropriate (i.e., not too detailed or too coarse) for capturing possible 2-state and 3-state folding kinetics that may coexist in one protein. Indeed, the unique ability of our method to produce large sets of unrelated folding pathways may potentially provide crucial insight into some aspects of folding kinetics that are not available to other theoretical techniques.
Author: Robert Pilstål
Publisher: Linköping University Electronic Press
ISBN: 9176853470
Category :
Languages : en
Pages : 206
Get Book Here
Book Description
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.
Author: Wolfgang Alt
Publisher: Birkhäuser
ISBN: 303488043X
Category : Mathematics
Languages : en
Pages : 306
Get Book Here
Book Description
Polymer and cell dynamics play an important role in processes like tumor growth, metastasis, embryogenesis, immune reactions and regeneration. Based on an international workshop on numerical simulations of polymer and cell dynamics in Bad Honnef (Germany) in 2000, this volume provides an overview of the relevant mathematical and numerical methods, their applications and limits. Polymer and Cell Dynamics will be of interest to scientists and advanced undergraduates.
Author: Information Resources Management Association
Publisher: IGI Global
ISBN: 146663605X
Category : Computers
Languages : en
Pages : 1826
Get Book Here
Book Description
"Bioinformatics: Concepts, Methodologies, Tools, and Applications highlights the area of bioinformatics and its impact over the medical community with its innovations that change how we recognize and care for illnesses"--Provided by publisher.
