 |
|
rotein folding: Building a strong foundation
September 18, 2006Like a 1950's Detroit automaker, it appears that nature prefers to build its proteins around a solid, sturdy chassis.
A new study combining advanced computational modeling and cutting-edge experiments by molecular biologists at Rice University and Baylor College of Medicine suggests that the most stable parts of a protein are also the parts that fold first.
Nature refuses to choose between form and function when it comes to protein folding; each protein's function is directly related to its shape, and when proteins misfold - something that's known to occur in a number of diseases like Alzheimer's and Huntington's - they don't function as they should.
In the new study, scientists designed and tested a new computational approach that aimed to study proteins with known shapes in order to ascertain which of their parts were the most stable in the face of chemical and thermal fluctuations.
"We found that the most stable parts of the final, folded protein come together first during the folding," said co-author Pernilla Wittung-Stafshede, associate professor of biochemistry and cell biology and of chemistry. She said the findings could help both scientists who are attempting to design synthetic proteins with a particular shape and scientists who are attempting to associate the shape and function of naturally occurring proteins.
The computational approach tested in the experiment was developed by the research group of co-author Jianpeng Ma, associate professor of bioengineering at Rice and associate professor of biochemistry and molecular biology at Baylor College of Medicine. Ma's group, which mainly focuses on multi-scale protein structure modeling and prediction, developed highly accurate knowledge-based potential functions that made the current collaborative study possible.
"As far as we know, no one has ever used this type of knowledge-based, statistical approach to predict the stability cores of proteins," Ma said. "Our results suggest that thermodynamics and kinetics are closely correlated in proteins and appear to have co-evolved for optimizing both the folding rate and the stability of proteins."
Wittung-Stafshede's group, which specializes in experimental studies related to protein folding, tested the model's predictions against experimental data gathered for several forms of the protein azurin, a copper-containing protein that folds into a sandwich-like structure called a beta sheet, which is a common fold in nature that consists of two beta-sheets of amino-acid strands meshed together.
"In folding study the right combination of expertise in computational and experimental approaches is vital for success," Ma said. "Our collaborative team has set an excellent example for future study."
Rice University
Protein Folding Current Events and Protein Folding News RSSProlonged stress sparks ER to release calcium stores and induce cell death in aging-related diseases
Study shows prolonged stress sparks ER to release calcium stores and induce cell death in aging-related diseases such as atherosclerosis, diabetes and neurodegeneration.
Protein folding: Diverse methods yield clues
Rice University physicists have written the next chapter in an innovative approach for studying the forces that shape proteins -- the biochemical workhorses of all living things.
New computer simulation helps explain folding in important cellular protein
Most parts of living organisms come packaged with ribbons. The ribbons are proteins-chains of amino acids that must fold into three-dimensional structures to work properly.
Scientists find a biological 'fountain of youth' in new world bat caves
Scientists from Texas are batty over a new discovery which could lead to the single most important medical breakthrough in human history-significantly longer lifespans.
Structural biology scores with protein snapshot
In a landmark technical achievement, investigators in the Vanderbilt Center for Structural Biology have used nuclear magnetic resonance (NMR) methods to determine the structure of the largest membrane-spanning protein to date.
Faster protein folding achieved through nanosecond pressure jump
A new method to induce protein folding by taking the pressure off of proteins is up to 100 times faster than previous methods, and could help guide more accurate computer simulations for how complex proteins fold.
Scripps research scientists 'watch' as individual alpha-synuclein proteins change shape
In an Early Edition publication of The Proceedings of the National Academy of Sciences (PNAS) this week, the researchers demonstrate the "alpha-synuclein dance" - the switching back and forth of the protein between a bent helix and an extended helix as the surface that it is binding to changes.
Caltech scientists find evidence for precise communication across brain areas during sleep
By listening in on the chatter between neurons in various parts of the brain, researchers from the California Institute of Technology (Caltech) have taken steps toward fully understanding just how memories are formed, transferred, and ultimately stored in the brain--and how that process varies throughout the various stages of sleep.
Caltech and UCSD researchers shed light on how proteins find their shapes
Researchers from the California Institute of Technology (Caltech) and the University of California at San Diego (UCSD) have brought together UCSD theoretical modeling and Caltech experimental data to show just how amino-acid chains might fold up into unique, three-dimensional functional proteins.
New open-source software permits faster desktop computer simulations of molecular motion
Whether vibrating in place or taking part in protein folding to ensure cells function properly, molecules are never still. Simulating molecular motions provides researchers with information critical to designing vaccines and helps them decipher the bases of certain diseases, such as Alzheimer's and Parkinson's, that result from molecular motion gone awry.
More Protein Folding Current Events and Protein Folding News Articles
 |
Lectures On Statistical Physics And Protein Folding by Kerson Huang (Author) This book introduces an approach to protein folding from the point of view of kinetic theory. There is an abundance of data on protein folding, but few proposals are available on the mechanism driving the process. Here, presented for the first time, are suggestions on possible research directions, as developed by the author in collaboration with C C Lin. The first half of this invaluable book contains a concise but relatively complete review of relevant topics in statistical mechanics and kinetic theory. It includes standard topics such as thermodynamics, the Maxwell–Boltzmann distribution, and ensemble theory. Special discussions include the dynamics of phase transitions, and Brownian motion as an illustration of stochastic processes. The second half develops topics in... |
 |
Protein Folding, Misfolding and Aggregation: Classical Themes and Novel Approaches (RSC Biomolecular Sciences) by Victor Muñoz (Editor) This unique book covers all the modern approaches and the many advances experienced in the field during the last 10 years. There is much emphasis on computational methods and studies of protein aggregation which have really flourished in the last decade. It includes chapters in the areas that have witnessed major developments and written by top experts including: computer simulations of folding, fast folding, single molecule spectroscopy, protein design, aggregation studies (both computational and experimental). |
 |
Protein Folding by Thomas E. Creighton (Author) The phenomenon of protein folding has become the focus of intense scientific inquiry. Researchers have realised the importance of understanding how proteins adopt their folding conformations, and are developing experimental techniques to attack this problem. , Protein Folding is a report on the current state of this crucial area of research-the 4y experiments, techniques, and implications of recent findings on modem biotechnology and biomedicine. Its authors are the world's leading investigators in this field, including: R M. Richards, Department of Molecular Biophysics and Biochemistry, Yale University - Janet M Thornton, Biomolecular Structure and Modelling Unit, University College,. . London, UK - Peter L Privokv, Institute of Protein Research, Academy of Sciences, Moscow - Martin... |
 |
Protein Folding Kinetics: Biophysical Methods by Bengt Nölting (Author) Protein Folding Kinetics - Biophysical Methods (2nd Edition) gives a deep insight into the principles and concepts of the kinetic and structural resolution of fast chemical and biophysical reactions of proteins with emphasis on protein-folding reactions. The study of fast protein-folding reactions and the understanding of the folding paradox have significantly advanced due to the recent development of new biophysical methods which allow not only kinetic resolution in the sub-millisecond time scale but also structural resolution with unprecedented precision. Pathways and structures of early and late folding events and the transition state structures of fast- and ultrafast-folding proteins can now be studied in far more detail. Important techniques include biophysical, chemical, molecular... |
 |
Protein Structure Prediction (Methods in Molecular Biology) by Mohammed Zaki (Editor), Chris Bystroff (Editor) This book covers elements of both the data-driven comparative modeling approach to structure prediction and also recent attempts to simulate folding using explicit or simplified models. Despite the unsolved mystery of how a protein folds, advances are being made in predicting the interactions of proteins with other molecules, such as small ligands, nucleic acids or other proteins. Also rapidly advancing are the methods for solving the inverse folding problem, the problem of finding a sequence to fit a structure. This book focuses on the various computational methods for prediction, their successes and their limitations, from the perspective of their most well known practitioners. |
 |
Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection (Heat Shock Proteins) by Alexzander A.A. Asea (Author), Alexzander A.A. Asea (Editor), Ian R. Brown (Editor) With the prevalence of neurodegenerative diseases on the rise as average life expectancy increases, the hunt for effective treatments and preventive measures for these disorders is a pressing challenge. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis have been termed 'protein misfolding disorders' that are characterized by the neural accumulation of protein aggregates. Manipulation of the cellular stress response involving the induction of heat shock proteins offers a therapeutic strategy to counter conformational changes in neural proteins that trigger pathogenic cascades resulting in neurodegenerative diseases. Heat shock proteins are protein repair agents that provide a line of defense against misfolded,... |
 |
Structure and Mechanism in Protein Science: A Guide to Enzyme Catalysis and Protein Folding by Alan Fersht (Author) Fersht’s Structure and Mechanism in Protein Science is a defining exploration of this new era, an expert depiction of the core principles of protein structure, activity, and mechanism as understood and applied today. A thorough recasting of Fersht’s previous text, the book takes a more general look at mechanisms in protein science, emphasizing the unity of concepts in folding and catalysis and the importance of the relationships between basic chemistry, kinetics, thermodynamics, and structure. |
 |
Foldases: Enzymes Catalyzing Protein Folding (Molecular Anatomy and Physiology of Proteins) by Natalya K. Nagradova (Editor) A great deal of talent has been called upon over the past decade to try and understand the structure and the function of different types of foldases; as a result, a remarkable insight into how these enzymes work has been gained. Recently the main focus of research has begun to shift to unveiling the precise role of these folding catalysts in many different processes in which they are involved inside the cell. It is becoming increasingly clear that the cellular functions of foldases go far beyond accelerating the folding of proteins. This is undoubtedly an area where one can expect significant research efforts in the next few years.The present book summarises the current state of knowledge as to the structural and functional properties of four major types of foldases listed above. In... |
 |
Protein Misfolding, Aggregation and Conformational Diseases: Part A: Protein Aggregation and Conformational Diseases (Protein Reviews) by Vladimir N. Uversky (Editor), Anthony L. Fink (Editor) This volume fills the gap in protein review and protocal literature while summarizing recent achievements in the understanding of the relationships between protein misfoldings, aggregation, and development of protein deposition disorders. It is devoted to the general questions of conformational disorders and includes discussion of involvement of such common factors as molecular chaperones, oxidative damage, proteasome, glycosoaminoglycans, serum amyloid protein P and several others in the development of different disorders. Some experimental techniques applicable for the visualization of protein deposition in vivo and in vitro are also present. |
 |
Aspects of Physical Biology: Biological Water, Protein Solutions, Transport and Replication (Lecture Notes in Physics) by G. Franzese (Editor), M. Rubi (Editor) The application to Biology of the methodologies developed in Physics is attracting an increasing interest from the scientific community. It has led to the emergence of a new interdisciplinary field, called Physical Biology, with the aim of reaching a better understanding of the biological mechanisms at molecular and cellular levels. Statistical Mechanics in particular plays an important role in the development of this new field. For this reason, the XXth session of the famous Sitges Conference on Statistical Physics was dedicated to "Physical Biology: from Molecular Interactions to Cellular Behavior". As is by now tradition, a number of lectures were subsequently selected, expanded and updated for publication as lecture notes, so as to provide both a state-of-the-art... |
| © 2009 BrightSurf.com |