Download or read book Probing Structure and Dynamics of Membrane Proteins by Molecular Dynamics Simulation written by Zoe Li (Ph. D. in pharmaceutics) and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular dynamics (MD) simulation provides atomistic details of biomolecules’ behaviors and has become a pivotal tool in the study of protein structure, dynamics and drug discovery. In this thesis, MD simulations are used in combination with experimental results to address a variety of biological questions in three protein systems: the 5HT3A serotonin receptor, the acetylcholine binding receptor (AChBP), and the Insig (insulin-induced gene)-Scap (SREBP (sterol regulatory element-binding protein)-cleavage activating protein) complex. The objective of our first system is to investigate the key to generating a stable open structure of the 5HT3A serotonin receptor based on low resolution cryo-electron microscopy structures, which may also apply to other pentameric ligand-gated ion channels (pLGICs). We developed a refined equilibration protocol that involves the rearrangement of transmembrane helices to achieve stable open state structures of the 5-HT3 receptor that allow both water and ion permeation through the channel. Our study underscores the importance of the conformational coupling between the transmembrane helices in stabilizing open-like state structures of the 5-HT3 receptor. Our second system aims to shed light on the nature of ligand recognition in the pLGICs that are activated upon ligand binding to their extracellular domains. The MD simulation-based absolute binding free energy calculation was carried out to study the electrostatic contribution in the binding of nicotine in a model system (AChBP). Finally, we performed extensive MD simulations on Scap to identify potential binding sites for a previously unknown SREBP activating molecule ammonia and to provide detailed structural mechanisms for how this molecule activates Scap.
Download or read book Characterization of Biological Membranes written by Mu-Ping Nieh and published by Walter de Gruyter GmbH & Co KG. This book was released on 2019-07-22 with total page 532 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of membranes has become of high importance in the fields of biology, pharmaceutical chemistry and medicine, since much of what happens in a cell or in a virus involves biological membranes. The current book is an excellent introduction to the area, which explains how modern analytical methods can be applied to study biological membranes and membrane proteins and the bioprocesses they are involved to.
Download or read book Probing the Mechanics of Protein Materials with Molecular Dynamics Simulations written by Senbo Xiao and published by . This book was released on 2011 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Membrane Organization and Dynamics written by Amitabha Chattopadhyay and published by Springer. This book was released on 2017-12-06 with total page 387 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume brings together information on membrane organization and dynamics from a variety of spectroscopic, microscopic and simulation approaches, spanning a broad range of time scales. The implication of such dynamic information on membrane function in health and disease is a topic of contemporary interest. The chapters cover various aspects of membrane lipid and protein dynamics, explored using a battery of experimental and theoretical approaches. The synthesis of information and knowledge gained by utilizing multiple approaches will provide the reader with a comprehensive understanding of the underlying membrane dynamics and function, which will help to develop robust dynamic models for the understanding of membrane function in healthy and diseased states. In the last few years, crystal structures of an impressive number of membrane proteins have been reported, thanks to tremendous advances in membrane protein crystallization techniques. Some of these recently solved structures belong to the G protein-coupled receptor (GPCR) family, which are particularly difficult to crystallize due to their intrinsic flexibility. Nonetheless, these static structures do not provide the necessary information to understand the function of membrane proteins in the complex membrane milieu. This volume will address the dynamic nature of membrane proteins within the membrane and will provide the reader with an up-to date overview of the theory and practical approaches that can be used. This volume will be invaluable to researchers working in a wide range of scientific areas, from biochemistry and molecular biology to biophysics and protein science. Students of these fields will also find this volume very useful. This book will also be of great use to those who are interested in the dynamic nature of biological processes.
Download or read book Combining Footprinting Mass Spectrometry and Molecular Dynamics Simulation for Structural Studies in Membrane Proteins written by Fengbo Zhou and published by . This book was released on 2018 with total page 94 pages. Available in PDF, EPUB and Kindle. Book excerpt: Membrane proteins are essential in many cellular processes and represent ~60% of all current drug targets. Due to technical limits, membrane proteins of various types were not studied extensively in the past and the biochemistry and functionality of them remain unclear. The structural biology methodologies require pure isolated protein samples for us to resolve their structure and study their biochemical functions. For such in vitro studies, however, membrane proteins often become unstable when isolated from their native lipid bilayer environment. To overcome the challenge, I employed a novel methodology of solubilizing membrane proteins in solution without detergent. I reconstituted ferroportin, an iron exporter, into saposin A lipoprotein discs, which provide a phospholipid bilayer environment for stabilizing the ferroportin. Those ferroportin picodiscs samples were further used for mass spectrometry footprinting experiments. Based on the analysis, different footprinting methods are an efficient and extensive probe of specific residues over the entire sequence of ferroportin. Footprinting results by fast photochemical oxidation of proteins (FPOP) show that the extramembrane regions of ferroportin in picodiscs are extensively oxidized by free hydroxyl radicals, whereas transmembrane regions are more protected, suggesting the native structure of ferroportin is retained throughout the labeling process. In contrast, footprinting by NEM, a membrane-permeable reagent, showed extensive labeling of cysteines in both the transmembrane (hydrophobic) regions and extramembrane (hydrophilic) regions. HDX digestion of ferroportin was done in ferroportin picodiscs and a ~92% sequence coverage was achieved for footprinting. Those results demonstrate saposin picodiscs to be a feasible tool for membrane protein studies with footprinting mass spectrometry methods.Because membrane proteins remain a challenge for experimental studies, I performed molecular dynamics (MD) simulation for studying membrane proteins and started a platform specifically for simulating membrane protein systems. I studied a variety of membrane protein systems including VKOR-warfarin binding, and HMGCR-UBIAD1 complex. Such work has provided mechanistic models to illustrate the binding protein-protein interactions and protein-ligand binding mechanisms in a phospholipid bilayer membrane.Those work are described in detail across all chapters. Chapter 1 serves as in introduction and overview of the MS and MD for membrane protein studies. Chapter 2 focuses on combining MS and MD to study human VKOR, and its binding mechanisms of VKOR-warfarin. Chapter 3 focuses on the preparation of the materials required for building saposin A picodiscs, and reconstituting membrane proteins into picodiscs. Chapter 4 and 5 present mass spectrometry studies and approaches of studying ferroportin picodiscs and its interaction with hepcidin, an inhibitive ligand of ferroportin. The manuscript of the work presented in those chapters is under preparation for publication. Chapter 6 describes a pure MD simulation study on I performed for building a UBIAD1-HMGCR binding model. Both UBIAD1 and HMGCR were generated with atomic models at best authority, with UBIAD1 generated as a homology model and HMGCR as a hybrid homology model. The manuscript of the work presented in Chapter 6 is finished and under preparation for publication.
Download or read book Computational Approaches for Understanding Dynamical Systems Protein Folding and Assembly written by and published by Academic Press. This book was released on 2020-03-05 with total page 554 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational Approaches for Understanding Dynamical Systems: Protein Folding and Assembly, Volume 170 in the Progress in Molecular Biology and Translational Science series, provides the most topical, informative and exciting monographs available on a wide variety of research topics. The series includes in-depth knowledge on the molecular biological aspects of organismal physiology, with this release including chapters on Pairwise-Additive and Polarizable Atomistic Force Fields for Molecular Dynamics Simulations of Proteins, Scale-consistent approach to the derivation of coarse-grained force fields for simulating structure, dynamics, and thermodynamics of biopolymers, Enhanced sampling and free energy methods, and much more. Includes comprehensive coverage on molecular biology Presents ample use of tables, diagrams, schemata and color figures to enhance the reader's ability to rapidly grasp the information provided Contains contributions from renowned experts in the field
Download or read book Molecular Simulations and Biomembranes written by Mark S P Sansom and published by Royal Society of Chemistry. This book was released on 2010-08-01 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: The need for information in the understanding of membrane systems has been caused by three things - an increase in computer power; methodological developments and the recent expansion in the number of researchers working on it worldwide. However, there has been no up-to-date book that covers the application of simulation methods to membrane systems directly and this book fills an important void in the market. It provides a much needed update on the current methods and applications as well as highlighting recent advances in the way computer simulation can be applied to the field of membranes and membrane proteins. The objectives are to show how simulation methods can provide an important contribution to the understanding of these systems. The scope of the book is such that it covers simulation of membranes and membrane proteins, but also covers the more recent methodological developments such as coarse-grained molecular dynamics and multiscale approaches in systems biology. Applications embrace a range of biological processes including ion channel and transport proteins. The book is wide ranging with broad coverage and a strong coupling to experimental results wherever possible, including colour illustrations to highlight particular aspects of molecular structure. With an internationally respected list of authors, its publication is timely and it will prove indispensable to a large scientific readership.
Download or read book Membrane Proteins written by Yosuke Senju and published by Mdpi AG. This book was released on 2024-01-26 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This reprint focuses on cutting-edge advancements and forthcoming prospects in membrane proteins. It encompasses the function, structure, and dynamics of membrane proteins from various perspectives, including cell biology, biochemistry, biophysics, structural biology, and molecular dynamics (MD) simulations.
Download or read book Protein Conformational Dynamics written by Ke-li Han and published by Springer Science & Business Media. This book was released on 2014-01-20 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses how biological molecules exert their function and regulate biological processes, with a clear focus on how conformational dynamics of proteins are critical in this respect. In the last decade, the advancements in computational biology, nuclear magnetic resonance including paramagnetic relaxation enhancement, and fluorescence-based ensemble/single-molecule techniques have shown that biological molecules (proteins, DNAs and RNAs) fluctuate under equilibrium conditions. The conformational and energetic spaces that these fluctuations explore likely contain active conformations that are critical for their function. More interestingly, these fluctuations can respond actively to external cues, which introduces layers of tight regulation on the biological processes that they dictate. A growing number of studies have suggested that conformational dynamics of proteins govern their role in regulating biological functions, examples of this regulation can be found in signal transduction, molecular recognition, apoptosis, protein / ion / other molecules translocation and gene expression. On the experimental side, the technical advances have offered deep insights into the conformational motions of a number of proteins. These studies greatly enrich our knowledge of the interplay between structure and function. On the theoretical side, novel approaches and detailed computational simulations have provided powerful tools in the study of enzyme catalysis, protein / drug design, protein / ion / other molecule translocation and protein folding/aggregation, to name but a few. This work contains detailed information, not only on the conformational motions of biological systems, but also on the potential governing forces of conformational dynamics (transient interactions, chemical and physical origins, thermodynamic properties). New developments in computational simulations will greatly enhance our understanding of how these molecules function in various biological events.
Download or read book Probing the Protein Dynamics by a Combination Approach of Molecular Dynamics Simulation with Time resolved Fluorescence Spectroscopy and X ray Scattering written by 楊承翰 and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Membrane Protein Structure and Dynamics written by Nagarajan Vaidehi and published by Humana Press. This book was released on 2012-09-14 with total page 357 pages. Available in PDF, EPUB and Kindle. Book excerpt: Membrane proteins play key roles in numerous cellular processes, in particular mediating cell-to-cell communication and signaling events that lead to a multitude of biological effects. Membrane proteins have also been implicated in many critical diseases such as atherosclerosis, hypertension, diabetes and cancer. In Membrane Protein Structure Predictions Methods: Methods and Protocols, expert researcher in the field detail the advances in both experimental and computational approaches of the structure, dynamics and interactions of membrane proteins dividing the volume into two sections. The first section details the procedures used for measurements of structure and dynamics of membrane proteins. While the second section contains a survey of the computational methods that have played a critical role in membrane protein structure prediction as well as in providing atomic level insight into the mechanism of the dynamics of membrane receptors. Written in the highly successful Methods in Molecular BiologyTM series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Membrane Protein Structure Predicitons: Methods and Protocols seeks to aid scientists in the further study of membrane protein structure and function.
Download or read book Biophysical Analysis of Membrane Proteins written by Eva Pebay-Peyroula and published by John Wiley & Sons. This book was released on 2008-06-25 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt: Meeting the need for a book on developing and using new methods to investigate membrane proteins, this is the first of its kind to present the full range of novel techniques in one resource. Top researchers from around the world focus on the physical principles exploited in the different techniques, and provide examples of how these can bring about important new insights. Following an introduction, further sections discuss structural approaches, molecular interaction and large assemblies, dynamics and spectroscopies, finishing off with an exploration of structure-function relationships in whole cells.
Download or read book Molecular Dynamics of Biomembranes written by Jos A.F.op den Kamp and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 419 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein insertion and translocation, intracellular traffic and sorting of membranes and their components, and lipid-protein interactions were the main topics of the Advanced Study Institute on "Molecular Dynamics of Membranes", which was held in June 1995 in Cargese, Corsica, France. The course, co-sponsored by NATO and FEBS, was the fifth in a series that started in 1987 and takes place every two years in the Institut d'Etudes Scientifiques in Cargese. This Institute, ideally situated and fully equiped for this type of scientific meeting has greatly contributed to the great success of the courses. Of course, also the outstanding contributions of a large number of well known scientists and the enthousiastic participation of excellent graduate students and postdocs has given the "Cargese Lectures on Biomembranes" a firm reputation in the scientific community. The present proceedings is more than just a reflection on the information presented in the Course. First of all it contains a number of extensive reviews of specific areas of interest. Noteworthy are the articles dealing with: • the general mechanisms of protein transport, the roles of invariant chain in antigen presentation, protein import and export in E. coli, protein folding and the role of chaperones, chloroplast and mitochondrial protein import, • membrane traffic in general and during mitosis, and with respect to membrane lipids: lipid domain formation, lipases: an extensive review about structure and properties, phospholipase A2 and bioactive lipids, phospholipid transfer proteins, • phospholipid localization and mobility and, finally, new strategies for protein reconstitution.
Download or read book Computational Biophysics of Membrane Proteins written by Carmen Domene and published by Royal Society of Chemistry. This book was released on 2016-11-30 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: Exploring current themes in modern computational and membrane protein biophysics, this book presents a comprehensive account of the fundamental principles underlying different methods and techniques used to describe the intriguing mechanisms by which membrane proteins function. The book discusses the experimental approaches employed to study these proteins, with chapters reviewing recent crucial structural advances that have allowed computational biophysicists to discern how these molecular machines work. The book then explores what computational methods are available to researchers and what these have taught us about three key families of membrane proteins: ion channels, transporters and receptors. The book is ideal for researchers in computational chemistry and computational biophysics.
Download or read book Protein Structure and Dynamics Studied by Molecular Dynamics Simulations written by Tim Meyer and published by . This book was released on 2008 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Using Molecular Dynamics to Probe Protein Conformational Transition Mechanisms at the Membrane Surface written by and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Structure Based Drug Discovery written by Leslie W. Tari and published by Humana Press. This book was released on 2012-01-06 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The last decade has seen the confluence of several enabling technologies that have allowed protein crystallographic methods to live up to their true potential. Taken together, the numerous recent advances have made it possible to tackle difficult biological targets with a high probability of success: intact bacterial ribosomes have been structurally elucidated, as well as eukaryotic trans-membrane proteins like the potassium channel and GPCRs. It is now possible for medicinal chemists to have access to structural information on their latest small molecule candidates bound to the therapeutic target within days of compound synthesis, allowing structure guided ligand optimization to occur in "real time". Structure-Based Drug Discovery presents an array of methods used to generate crystal structures of biological macromolecules, how to leverage the structural information to design novel ligands anew, and how to iteratively optimize hits and convert them to leads. Written in the successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Structure-Based Drug Discovery aims to provide scientists interested in adding SBDD to their arsenal of drug discovery methods with well-honed, up-to-date methodologies.
