Science

Protein Dynamics, Function, and Design

Author: Oleg Jardetzky

Publisher: Springer Science & Business Media

ISBN:

Category: Science

Page: 222

View: 202

This volume is a collection of articles from the proceedings of the International School of Structural Biology and Magnetic Resonance 3rd Course: Protein Dynamics, Function, and Design. This NATO Advance Study Institute was held in Erice at the Ettore Majorana Centre for Scientific Culture on April 16-28, 1997. The aim of the Institute was to bring together experts applyipg different physical methods to problems of macro molecular dynamics-notably x-ray diffraction, NMR and other forms of spectroscopy, and molecular dynamics simulations. Emphasis was placed on those systems and types of problems-such as mechanisms of allosteric control, signal transmission, induced fit to different ligands with its implications for drug design, and the effects of dynamics on structure determination-where a correlation of findings obtained by different methods could shed the most light on the mechanisms involved and stimulate the search for new approaches. The individual articles represent the state of the art in each of the areas cov ered and provide a guide to the original literature in this rapidly developing field. v CONTENTS 1. Determining Structures of ProteinlDN A Complexes by NMR Angela M. Gronenbom and G. Marius Clore 2. Fitting Protein Structures to Experimental Data: Lessons from before Your Mother Was Born . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Jeffrey C. Hoch, Alan S. Stem, and Peter J. Connolly 3. Multisubunit Allosteric Proteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 William N. Lipscomb 4. Studying Protein Structure and Function by Directed Evolution: Examples with Engineered Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Andreas Pliickthun 5. High Pressure Effects on Protein Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Science

Computational Approaches to Protein Dynamics

Author: Monika Fuxreiter

Publisher: CRC Press

ISBN:

Category: Science

Page: 479

View: 236

The Latest Developments on the Role of Dynamics in Protein Functions Computational Approaches to Protein Dynamics: From Quantum to Coarse-Grained Methods presents modern biomolecular computational techniques that address protein flexibility/dynamics at all levels of theory. An international contingent of leading researchers in chemistry, physics, and biology show how these advanced methods provide insights into dynamic aspects of biochemical processes. A particular focus is on intrinsically disordered proteins (IDPs), which lack a well-defined three-dimensional structure and function as dynamic ensembles. The book covers a wide spectrum of dynamics, from electronic structure-based to coarse-grained techniques via multiscaling at different levels. After an introduction to dynamics and historical overview of basic methodologies, the book addresses the following issues: Is there a quantitative relationship between enzymatic catalysis and protein dynamics? Which are the functionally relevant motions of proteins? How can structural properties and partner recognition mechanisms of IDPs be simulated? How can we speed up molecular dynamics? How can we describe conformational ensembles by the synergistic effort of computations and experiments? While dynamics is now considered essential for interpreting protein action, it is not yet an integral component in establishing structure–function relationships of proteins. Helping to reshape this classical view in biochemistry, this groundbreaking book explores advances in computational methodology and contributes to the new, ensemble way of studying proteins.
Science

Protein Dynamics

Author: Dennis R. Livesay

Publisher: Humana Press

ISBN:

Category: Science

Page: 285

View: 491

In Protein Dynamics: Methods and Protocols, expert researchers in the field detail both experimental and computational methods to interrogate molecular level fluctuations. Chapters detail best-practice recipes covering both experimental and computational techniques, reflecting modern protein research. Written in the highly 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 laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Protein Dynamics: Methods and Protocols describes the most common and powerful methods used to characterize protein dynamics.
Science

Proteins

Author: Charles L. Brooks

Publisher: John Wiley & Sons

ISBN:

Category: Science

Page: 259

View: 479

Presenting a wide-ranging view of current developments in protein research, the papers in this collection, each written by highly regarded experts in the field, examine various aspects of protein structure, functions, dynamics, and experimentation. Topics include dynamical simulation methods, the biological role of atom fluctuations, protein folding, influences on protein dynamics, and a variety of analytical techniques, such as X-ray diffraction, vibrational spectroscopy, photodissociation and rebinding kinetics. This is part of a series devoted to providing general information on a wide variety of topics in chemical physics in order to stimulate new research and to serve as a text for beginners in a particular area of chemical physics.
Electronic books

Improved Methods for Characterization of Protein Dynamics by NMR spectroscopy and Studies of the EphB2 Kinase Domain

Author: Alexandra Ahlner

Publisher: Linköping University Electronic Press

ISBN:

Category: Electronic books

Page: 58

View: 286

Proteins are essential for all known forms of life and in many lethal diseases protein failure is the cause of the disease. To understand proteins and the processes they are involved in, it is valuable to know their structures as well as their dynamics and interactions. The structures may not be directly inspected because proteins are too small to be visible in a light microscope, which is why indirect methods such as nuclear magnetic resonance (NMR) spectroscopy have to be utilized. This method provides atomic information about the protein and, in contrast to other methods with similar resolution, the measurements are performed in solution resulting in more physiological conditions, enabling analysis of dynamics. Important dynamical processes are the ones on the millisecond timeframe, which may contribute to interactions of proteins and their catalysis of chemical reactions, both of significant value for the function of the proteins. To better understand proteins, not only do we need to study them, but also develop the methods we are using. This thesis presents four papers about improved NMR techniques as well as a fifth where the kinase domain of ephrinB receptor 2 (EphB2) has been studied regarding the importance of millisecond dynamics and interactions for the activation process. The first paper presents the software COMPASS, which combines statistics and the calculation power of a computer with the flexibility and experience of the user to facilitate and speed up the process of assigning NMR signals to the atoms in the protein. The computer program PINT has been developed for easier and faster evaluation of NMR experiments, such as those that evaluate protein dynamics. It is especially helpful for NMR signals that are difficult to distinguish, so called overlapped peaks, and the soft- ware also converts the detected signals to the indirectly measured physical quantities, such as relaxation rate constants, principal for dynamics. Next are two new versions of the Carr-Purcell-Maiboom-Gill (CPMG) dispersion pulse sequences, designed to measure millisecond dynamics in a way so that the signals are more separated than in standard experiments, to reduce problems with overlaps. To speed up the collection time of the data set, a subset is collected and the entire data set is then reconstructed, by multi-dimensional decomposition co-processing. Described in the thesis is also a way to produce suitably labeled proteins, to detect millisecond dynamics at C? positions in proteins, using the CPMG dispersion relaxation experiment at lower protein concentrations. Lastly, the kinase domain of EphB2 is shown to be more dynamic on the millisecond time scale as well as more prone to interact with itself in the active form than in the inactive one. This is important for the receptor function of the protein, when and how it mediates signals. To conclude, this work has extended the possibilities to study protein dynamics by NMR spectroscopy and contributed to increased understanding of the activation process of EphB2 and its signaling mechanism.
Hydration

Influence of Temperature and Hydration on Protein Dynamics

Author: Joon Ho Roh

Publisher:

ISBN:

Category: Hydration

Page: 194

View: 804

"Protein dynamics play a crucial role in protein function, since a protein needs to be protean in its conformations to fulfill its role as a biological machine (e.g. to act as an enzyme). A dynamic transition is believed to be closely related to the onset of protein activity that becomes measurable at temperatures above the dynamic transition temperature T(D). Hydration and temperature are two important parameters for both the dynamic transition and protein activity. However, the correlation between protein dynamics and protein function has not been clearly established and the microscopic mechanism of the dynamics activated above T(D) is still a subject of discussion. In our research, we used neutron and light scattering measurements to study the temperature and hydration dependence of protein (lysozyme) dynamics in the picosecond and nanosecond time window. We identified three main dynamic processes in protein molecules: i) methyl group rotation, ii) a fast process, and iii) a slow relaxation process. We demonstrated that the methyl group rotation is activated at T ~ 100 K regardless of hydration. Only wet proteins at hydration levels higher than 0.2 h (h = g of water per 1 g protein) exhibit the dynamic transition and the slow relaxation process, whereas the fast process is present even in proteins at hydration levels lower than 0.2 h. We showed that the slow relaxation process is responsible for the dynamic transition and is closely related to enzymatic activity. The temperature dependence of the slow relaxation process exhibits an Arrhenius-like behavior at T> T(D). This result suggests that the dynamic transition is just the results of the slow relaxation process entering the experimentally accessible time window. An analysis of the influence of solvents on protein dynamics suggests that glycerol suppresses the fast process of protein more strongly than do other solvents (e.g. water and trehalose) at T
Science

Protein Dynamics, Function, and Design

Author: Oleg Jardetzky

Publisher: Springer

ISBN:

Category: Science

Page: 222

View: 896

This volume is a collection of articles from the proceedings of the International School of Structural Biology and Magnetic Resonance 3rd Course: Protein Dynamics, Function, and Design. This NATO Advance Study Institute was held in Erice at the Ettore Majorana Centre for Scientific Culture on April 16-28, 1997. The aim of the Institute was to bring together experts applyipg different physical methods to problems of macro molecular dynamics-notably x-ray diffraction, NMR and other forms of spectroscopy, and molecular dynamics simulations. Emphasis was placed on those systems and types of problems-such as mechanisms of allosteric control, signal transmission, induced fit to different ligands with its implications for drug design, and the effects of dynamics on structure determination-where a correlation of findings obtained by different methods could shed the most light on the mechanisms involved and stimulate the search for new approaches. The individual articles represent the state of the art in each of the areas cov ered and provide a guide to the original literature in this rapidly developing field. v CONTENTS 1. Determining Structures of ProteinlDN A Complexes by NMR Angela M. Gronenbom and G. Marius Clore 2. Fitting Protein Structures to Experimental Data: Lessons from before Your Mother Was Born . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Jeffrey C. Hoch, Alan S. Stem, and Peter J. Connolly 3. Multisubunit Allosteric Proteins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 William N. Lipscomb 4. Studying Protein Structure and Function by Directed Evolution: Examples with Engineered Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Andreas Pliickthun 5. High Pressure Effects on Protein Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Materials science

Influence of Solvent on Protein Dynamics and Activity

Author: Sheila Khodadadi

Publisher:

ISBN:

Category: Materials science

Page: 206

View: 829

"The microscopic picture of protein dynamics provides insight into the protein functionality. It was accepted earlier by many researchers that protein dynamics and activity are related to the solvent and its viscosity. However the detailed mechanism of the solvent-protein interactions is not fully understood. On the other hand, a connection between the appearance of measurable activity and the "dynamic transition" in proteins has been observed. The "dynamic transition" is marked by a sharp rise in the mean squared atomic displacement r2, in proteins occurring at TD ~ 200-230 K. Many contradicting models have been proposed to describe the origin of this phenomenon including a recent idea that relates it to the sudden change in a property of the hydration water. After decades of studies, the origin of the dynamic transition and the role of solvent in protein dynamics remain a subject of active discussions. Combining dielectric spectroscopy and neutron scattering techniques, we are able to follow protein dynamics over an extremely broad frequency and temperature range. We identify several relaxation processes in dielectric spectra of the hydrated lysozyme. We assign the main observed dielectric relaxation process to the structural relaxation of the protein-water coupled motion. Based on analysis of neutron spectroscopy and simulations results, we ascribe the slower dielectric relaxation process to a global large-scale motion of the protein. We demonstrate that the sharp rise in r2 is just a result of the protein-water coupled relaxation reaching the limit of the experimental frequency window of the neutron spectrometer. Our results show no sharp change in temperature variation of the structural relaxation of both the protein and its hydration water. Light scattering measurements of hydrated lysozyme indicate a broad glass transition at Tg ~ 180[plus or minus]15 K. We emphasize that the dynamic transition (as measured by mean squared atomic displacement) and the glass transition of the system happening at Tg ~ 180[plus or minus]15 K are not the same phenomena. A strong coupling of protein activity and its dynamics has been observed in protein solutions in glycerol-water and in sucrose-water. The analysis, however, indicates that protein dynamics and its activity are not always coupled to the solvent viscosity. The microscopic mechanism of this decoupling remains unclear."--Abstract.