Dynameomics: protein dynamics and unfolding across fold space

2010 ◽  
Vol 1 (5-6) ◽  
pp. 335-344
Author(s):  
Amanda L. Jonsson ◽  
R. Dustin Schaeffer ◽  
Marc W. van der Kamp ◽  
Valerie Daggett
Keyword(s):  
Protein Folding ◽  
Protein Dynamics ◽  
Large Set ◽  
Protein Fold ◽  
Structural Elements ◽  
Native State ◽  
Reversible Process ◽  
Different Types ◽  
Protein Fold Space ◽  
Β Sheet

AbstractAll currently known structures of proteins together define ‘protein fold space’. To increase the general understanding of protein dynamics and protein folding, we selected a set of 807 proteins and protein domains that represent 95% of the currently known autonomous folded domains present in globular proteins. Native state and unfolding simulations of these representatives are now complete and accessible via a novel database containing over 11 000 simulations. Because protein folding is a microscopically reversible process, these simulations effectively sample protein folding across all of protein fold space. Here, we give an overview of how the representative proteins were selected and how the simulations were performed and validated. We then provide examples of different types of analyses that can be performed across our large set of simulations, made possible by the database approach. We further show how the unfolding simulations can be used to compare unfolding of structural elements in isolation and in different structural contexts, using as an example a short, triple stranded β-sheet that forms the WW domain and is present in several larger unrelated proteins.

scholarly journals Pulse labeling reveals the tail end of protein folding by proteome profiling

2021 ◽  
Author(s):  
Mang Zhu ◽  
Erich R. Kuechler ◽  
Nikolay Stoynov ◽  
Joerg Gsponer ◽  
Thibault Mayor
Keyword(s):  
Mass Spectrometry ◽  
Protein Folding ◽  
Heat Stress ◽  
Protein Complexes ◽  
Protein Sequences ◽  
Protein Homeostasis ◽  
Native State ◽  
Binding Motifs ◽  
Specific Subset ◽  
Β Sheet

SummaryAccurate and efficient folding of nascent protein sequences into their native state requires support from the protein homeostasis network. Herein we probed which newly translated proteins are less thermostable to infer which polypeptides require more time to fold within the proteome. Specifically, we determined which of these proteins were more susceptible to misfolding and aggregation under heat stress using pulse SILAC coupled mass spectrometry. These proteins are abundant, short, and highly structured. Notably these proteins display a tendency to form β-sheet structures, a configuration which typically requires more time for folding, and were enriched for Hsp70/Ssb and TRiC/CCT binding motifs, suggesting a higher demand for chaperone-assisted folding. These polypeptides were also more often components of stable protein complexes in comparison to other proteins. All evidence combined suggests that a specific subset of newly translated proteins requires more time following synthesis to reach a thermostable native state in the cell.

scholarly journals Protein folding guides disulfide bond formation

2015 ◽  
Vol 112 (36) ◽  
pp. 11241-11246 ◽  
Author(s):  
Meng Qin ◽  
Wei Wang ◽  
D. Thirumalai
Keyword(s):  
Protein Folding ◽  
Disulfide Bond ◽  
Disulfide Bonds ◽  
Broad Class ◽  
Bond Formation ◽  
Coarse Grained ◽  
Disulfide Bond Formation ◽  
Native State ◽  
Experimental Findings ◽  
Β Sheet

The Anfinsen principle that the protein sequence uniquely determines its structure is based on experiments on oxidative refolding of a protein with disulfide bonds. The problem of how protein folding drives disulfide bond formation is poorly understood. Here, we have solved this long-standing problem by creating a general method for implementing the chemistry of disulfide bond formation and rupture in coarse-grained molecular simulations. As a case study, we investigate the oxidative folding of bovine pancreatic trypsin inhibitor (BPTI). After confirming the experimental findings that the multiple routes to the folded state contain a network of states dominated by native disulfides, we show that the entropically unfavorable native single disulfide [14–38] between Cys14 and Cys38 forms only after polypeptide chain collapse and complete structuring of the central core of the protein containing an antiparallel β-sheet. Subsequent assembly, resulting in native two-disulfide bonds and the folded state, involves substantial unfolding of the protein and transient population of nonnative structures. The rate of [14–38] formation increases as the β-sheet stability increases. The flux to the native state, through a network of kinetically connected native-like intermediates, changes dramatically by altering the redox conditions. Disulfide bond formation between Cys residues not present in the native state are relevant only on the time scale of collapse of BPTI. The finding that formation of specific collapsed native-like structures guides efficient folding is applicable to a broad class of single-domain proteins, including enzyme-catalyzed disulfide proteins.

Non-native local interactions in protein folding and stability: introducing a helical tendency in the all β-sheet α-spectrin SH3 domain

1997 ◽  
Vol 268 (4) ◽  
pp. 760-778 ◽  
Author(s):  
Jesús Prieto ◽  
Matthias Wilmans ◽  
Marı́a Angeles Jiménez ◽  
Manuel Rico ◽  
Luis Serrano
Keyword(s):  
Protein Folding ◽  
Sh3 Domain ◽  
Local Interactions ◽  
Β Sheet

scholarly journals Early-Age Cracking in Concrete: Causes, Consequences, Remedial Measures, and Recommendations

2018 ◽  
Vol 8 (10) ◽  
pp. 1730 ◽  
Author(s):  
Md. Safiuddin ◽  
A. Kaish ◽  
Chin-Ong Woon ◽  
Sudharshan Raman
Keyword(s):  
Service Life ◽  
Concrete Structures ◽  
Real Life ◽  
Early Age ◽  
Structural Elements ◽  
Remedial Measures ◽  
Curing Conditions ◽  
Factors Affecting ◽  
Different Types ◽  
Service Conditions

Cracking is a common problem in concrete structures in real-life service conditions. In fact, crack-free concrete structures are very rare to find in real world. Concrete can undergo early-age cracking depending on the mix composition, exposure environment, hydration rate, and curing conditions. Understanding the causes and consequences of cracking thoroughly is essential for selecting proper measures to resolve the early-age cracking problem in concrete. This paper will help to identify the major causes and consequences of the early-age cracking in concrete. Also, this paper will be useful to adopt effective remedial measures for reducing or eliminating the early-age cracking problem in concrete. Different types of early-age crack, the factors affecting the initiation and growth of early-age cracks, the causes of early-age cracking, and the modeling of early-age cracking are discussed in this paper. A number of examples for various early-age cracking problems of concrete found in different structural elements are also shown. Above all, some recommendations are given for minimizing the early-age cracking in concrete. It is hoped that the information conveyed in this paper will be beneficial to improve the service life of concrete structures. Concrete researchers and practitioners may benefit from the contents of this paper.

Self-Similarity of Protein Folding Flows

2012 ◽  
Vol 7 (4) ◽  
pp. 136-141
Author(s):  
I. Kalgin ◽  
Sergey Chekmarev
Keyword(s):  
Protein Folding ◽  
Sh3 Domain ◽  
Atomic Level ◽  
The Self ◽  
Coarse Grained ◽  
Folding Kinetics ◽  
Native State ◽  
Self Similarity ◽  
Folding Dynamics ◽  
Fractal Character

The problem of how a protein folds into its functional (native) state is one of the central problems of molecular biology, which attracts the attention of researchers from biology, physics and chemistry for many years. Of particular interest are general properties of the folding process, because the mechanisms of folding of different proteins can be essentially different. Previously, in the study of folding of fyn SH3 domain, we found that despite all the diversity and complexity of individual folding trajectories, the folding flows possess a well pronounced property of self-similarity, with a fractal character of the flow distributions. In the present paper, we study this phenomenon for another protein – beta3s, which is essentially different from the SH3 domain in its structure and folding kinetics. Also, in contrast to the fyn SH3 domain, for which a coarse-grained representation was used, we perform simulations on the atomic level of resolution. We show that the self-similarity and fractality of folding flows are observed is this case too, which suggests that these properties are characteristic of the protein folding dynamics

An Evaluation and Comparison of Models for Maximum Deflection of Stiffened Plates Using Finite Element Analysis

2007 ◽  
Vol 44 (04) ◽  
pp. 212-225
Author(s):  
Lior Banai ◽  
Omri Pedatzur
Keyword(s):  
Finite Element ◽  
Orthotropic Plate ◽  
Lateral Pressure ◽  
Stiffened Plates ◽  
Maximum Deflection ◽  
Structural Elements ◽  
The Finite Element Method ◽  
Element Analysis ◽  
The Past ◽  
Different Types

Stiffened plates form the backbone of most of a ship's structure. Today, finite element (FE) models are used to analyze the behavior of such structural elements for different types of loads. In the past, when usage of computers and FE models were not used very much, analytical analysis methods were required. Two well-known methods have been developed for analyses of stiffened plates under lateral loading (uniform pressure), based on two different models, namely, the orthotropic plate model and the grillage model. Both models can give estimations for the maximum plate deflection under uniform lateral pressure. The objective of this paper is to present the two methods, evaluate and compare the methods using the finite element method, and finally implement the methods as a computer program for quick estimations of the maximum deflection of stiffened plates. The degree of accuracy of the two methods when compared to FE is discussed in some detail.

scholarly journals Globalization of the transport system of the agro-industrial complex in the conditions of modern society

2020 ◽  
Vol 176 ◽  
pp. 05020
Author(s):  
M.A. Ananyev ◽  
Zh.Yu Bakaeva ◽  
O.L. Matveeva ◽  
I.V. Steklova ◽  
E.N. Shchegoleva
Keyword(s):  
Transport System ◽  
Modern Society ◽  
Transport Systems ◽  
Industrial Complex ◽  
Structural Elements ◽  
Economic Space ◽  
Different Types ◽  
Food Market ◽  
Temporal And Spatial ◽  
Favorable Conditions

The article deals with the problem of transportation of agricultural products. The main causes of problems in this area are identified. The mechanism of creating favorable conditions in the system of globalization relations of the modern economy is analyzed. The fundamental elements in the transport system are competition orientation and information ownership over a certain period of time. Globalization involves the integration of different types of transport systems at the sectoral characteristics. The purpose of the research is to study the essence, meaning and prospects of the concept of “economic transport space in the national food supply system" in the processes of food market globalization. The main indicators of the “economic space" are: first, to determine the parameters that characterize the economic transport space, and secondly, to determine the prospects for using its structural elements in the system of transport supply relations, depending on the temporal and spatial components in the modern sector of the economy to provide food for the needs of society.

scholarly journals Protein folding while chaperone bound is dependent on weak interactions

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kevin Wu ◽  
Frederick Stull ◽  
Changhan Lee ◽  
James C. A. Bardwell
Keyword(s):  
Protein Folding ◽  
Weak Interactions ◽  
Client Protein ◽  
Native State ◽  
Folding Rate ◽  
Sufficient Strength ◽  
Surprising Observation

Abstract It is generally assumed that protein clients fold following their release from chaperones instead of folding while remaining chaperone-bound, in part because binding is assumed to constrain the mobility of bound clients. Previously, we made the surprising observation that the ATP-independent chaperone Spy allows its client protein Im7 to fold into the native state while continuously bound to the chaperone. Spy apparently permits sufficient client mobility to allow folding to occur while chaperone bound. Here, we show that strengthening the interaction between Spy and a recently discovered client SH3 strongly inhibits the ability of the client to fold while chaperone bound. The more tightly Spy binds to its client, the more it slows the folding rate of the bound client. Efficient chaperone-mediated folding while bound appears to represent an evolutionary balance between interactions of sufficient strength to mediate folding and interactions that are too tight, which tend to inhibit folding.

scholarly journals Exploring Protein Fold Space

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 193 ◽  
Author(s):  
William R. Taylor
Keyword(s):  
Protein Structures ◽  
Pairwise Comparison ◽  
Secondary Structures ◽  
Beta Sheets ◽  
Protein Fold ◽  
Helical Packing ◽  
Model Protein ◽  
Protein Fold Space ◽  
Open Question ◽  
Generate Model

The model of protein folding proposed by Ptitsyn and colleagues involves the accretion of secondary structures around a nucleus. As developed by Efimov, this model also provides a useful way to view the relationships among structures. Although somewhat eclipsed by later databases based on the pairwise comparison of structures, Efimov’s approach provides a guide for the more automatic comparison of proteins based on an encoding of their topology as a string. Being restricted to layers of secondary structures based on beta sheets, this too has limitations which are partly overcome by moving to a more generalised secondary structure lattice that can encompass both open and closed (barrel) sheets as well as helical packing of the type encoded by Murzin and Finkelstein on small polyhedra. Regular (crystalline) lattices, such as close-packed hexagonals, were found to be too limited so pseudo-latticses were investigated including those found in quasicrystals and the Bernal tetrahedron-based lattice that he used to represent liquid water. The Bernal lattice was considered best and used to generate model protein structures. These were much more numerous than those seen in Nature, posing the open question of why this might be.

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