Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sequence of events in folding mechanism: beyond the Go model.

ABSTRACT: Simplified G? models, where only native contacts interact favorably, have proven useful to characterize some aspects of the folding of small proteins. The success of these models is limited by the fact that all residues interact in the same way so that the folding features of a protein are determined only by the geometry of its native conformation. We present an extended version of a Calpha-based G? model where different residues interact with different energies. The model is used to calculate the thermodynamics of three small proteins (Protein G, Src-SH3, and CI2) and the effect of mutations (DeltaDeltaGU-N, DeltaDeltaGdouble dagger-N, DeltaDeltaGdouble dagger-U, and phi-values) on the wild-type sequence. The model allows us to investigate some of the most controversial areas in protein folding, such as its earliest stages and the nature of the unfolded state, subjects that have lately received particular attention.

SUBMITTER: Sutto L

PROVIDER: S-EPMC2242563 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Sequence of events in folding mechanism: beyond the Gō model.

Sutto Ludovico L Tiana Guido G Broglia Ricardo A RA

Protein science : a publication of the Protein Society 20060701 7

Simplified Gō models, where only native contacts interact favorably, have proven useful to characterize some aspects of the folding of small proteins. The success of these models is limited by the fact that all residues interact in the same way so that the folding features of a protein are determined only by the geometry of its native conformation. We present an extended version of a Calpha-based Gō model where different residues interact with different energies. The model is used to calculate t ...[more]

PMID: 16815916

Similar Datasets

Analyses of the folding sites of irregular ?-trefoil fold proteins through sequence-based techniques and Go-model simulations.

Project description:BackgroundThe details of the folding mechanisms have not yet been fully understood for many proteins, and it is believed that the information on the folding mechanism of a protein is encoded in its amino acid sequence. ?-trefoil proteins are known to have the same 3D scaffold, namely, a three-fold symmetric scaffold, despite the proteins' low sequence identity among superfamilies. In this study, we extract an initial folding unit from the amino acid sequences of irregular ?-trefoil proteins by constructing an average distance map (ADM) and utilizing inter-residue average distance statistics to determine the relative contact frequencies for residue pairs in terms of F values. We compare our sequence-based prediction results with the packing between hydrophobic residues in native 3D structures and a G?-model simulation.ResultsThe ADM and F-value analyses predict that the N-terminal and C-terminal regions are compact and that the hydrophobic residues at the central region can be regarded as an interaction center with other residues. These results correspond well to those of the G?-model simulations. Moreover, our results indicate that the irregular parts in the ?-trefoil proteins do not hinder the protein formation. Conserved hydrophobic residues on the ?5 strand are always the interaction center of packing between the conserved hydrophobic residues in both regular and irregular ?-trefoil proteins.ConclusionsWe revealed that the ?5 strand plays an important role in ?-trefoil protein structure construction. The sequence-based methods used in this study can extract the protein folding information from only amino acid sequence data, and well corresponded to 3D structure-based G?-model simulation and available experimental results.

| S-EPMC7477875 | biostudies-literature

The sequence of events during folding of a DNA origami.

Project description:We provide a comprehensive reference dataset of the kinetics of a multilayer DNA origami folding. To this end, we measured the folding kinetics of every staple strand and its two terminal segments during constant-temperature assembly of a multilayer DNA origami object. Our data illuminate the processes occurring during folding of the DNA origami in fine detail, starting with the first nucleating double-helical domains and ending with the fully folded DNA origami object. We found a complex sequence of folding events that cannot be explained with simplistic local design analysis. Our real-time data, although derived from one specific DNA origami object, through its sheer massive detail, could provide the crucial input needed to construct and test a quantitatively predictive, general model of DNA origami assembly.

| S-EPMC6499592 | biostudies-literature

Go hybrid: EM, crystallography, and beyond.

Project description:A mechanistic understanding of the molecular transactions that govern cellular function requires knowledge of the dynamic organization of the macromolecular machines involved in these processes. Structural biologists employ a variety of biophysical methods to study large macromolecular complexes, but no single technique is likely to provide a complete description of the structure-function relationship of all the constituent components. Since structural studies generally only provide snapshots of these dynamic machines as they accomplish their molecular functions, combining data from many methodologies is crucial to our understanding of molecular function.

| S-EPMC3478466 | biostudies-literature

Folding and association of a homotetrameric protein complex in an all-atom Go model.

Project description:The 84-residue homotetrameric BBAT1 is one of the smallest stable protein complexes and therefore is a good test system to study the self-assembly of multimeric proteins. We have researched for this protein the interplay between the folding of monomers and their assembly into tetramers. Replica exchange molecular dynamics simulations relying on a Go model are compared with earlier simulations that use the physics-based coarse-grained UNRES model.

| S-EPMC4201375 | biostudies-literature

Bioinformatics service center projects go beyond service.

Project description:To probe the complexity of modern diseases, multidisciplinary approaches are increasingly applied. Typically underpinning such studies are collaborations between wet bench experimentalists and dry lab bioinformaticians. Despite the need, bioinformatics collaborators remain difficult to find. Therefore, we undertook a study to understand the nature of this research, so that we may better understand how to meet the needs of future multidisciplinary projects. To accomplish this, we have performed a retrospective study of data from three years of projects performed by the UTHealth Bioinformatics Service Center. Based on this, we found that the bioinformatics in these collaborative projects are extremely diverse and require a high degree of intellectual engagement, while requiring only a small amount of publishable methods development. Very few of the specific skills, the strength of a service core, could be recycled across projects, which were generally exploratory and open-ended and required cycles of biological hypothesis development and (in silico) testing. We find that biomedical research requires bioinformaticians that are highly trained, having the ability to think biologically, but investigating using computational rather than bench experiments. This is in contrast to the activities that are typically the basis for an independent career in biomedical informatics, namely developing new software and algorithms. These findings suggest that to foster team-based multidisciplinary research, institutions must adopt policies that recognize contributions to research by applied bioinformatics scientists.

| S-EPMC6785826 | biostudies-literature

Scaling of folding properties in go models of proteins.

Project description:Insights about scaling of folding properties of proteins are obtained bystudying folding in heteropolymers described by Go-like Hamiltonians. Bothlattice and continuum space models are considered. In the latter case, themonomer-monomer interactions correspond to the Lennard-Jones potential.Several statistical ensembles of the two- and three-dimensional targetnative conformations are considered. Among them are maximally compactconformations which are confined to a lattice and those which are obtainedeither through quenching or annealing of homopolymers to their compactlocal energy minima. Characteristic folding times are found to grow aspower laws with the system size. The corresponding exponents are notuniversal. The size related deterioration of foldability is found to beconsistent with the scaling behavior of the characteristic temperatures:asymptotically, the folding temperature becomes much lower than thetemperature at which glassy kinetics become important. The helicalconformations are found to have the lowest overall scaling exponent andthe best foldability among the classes of conformations studied. Thescaling properties of the Go-like models of the protein conformationsstored in the Protein Data Bank suggest that proteins are not optimizedkinetically.

| S-EPMC3456313 | biostudies-other

Embeddings from deep learning transfer GO annotations beyond homology.

Project description:Knowing protein function is crucial to advance molecular and medical biology, yet experimental function annotations through the Gene Ontology (GO) exist for fewer than 0.5% of all known proteins. Computational methods bridge this sequence-annotation gap typically through homology-based annotation transfer by identifying sequence-similar proteins with known function or through prediction methods using evolutionary information. Here, we propose predicting GO terms through annotation transfer based on proximity of proteins in the SeqVec embedding rather than in sequence space. These embeddings originate from deep learned language models (LMs) for protein sequences (SeqVec) transferring the knowledge gained from predicting the next amino acid in 33 million protein sequences. Replicating the conditions of CAFA3, our method reaches an Fmax of 37?±?2%, 50?±?3%, and 57?±?2% for BPO, MFO, and CCO, respectively. Numerically, this appears close to the top ten CAFA3 methods. When restricting the annotation transfer to proteins with?<?20% pairwise sequence identity to the query, performance drops (Fmax BPO 33?±?2%, MFO 43?±?3%, CCO 53?±?2%); this still outperforms naïve sequence-based transfer. Preliminary results from CAFA4 appear to confirm these findings. Overall, this new concept is likely to change the annotation of proteins, in particular for proteins from smaller families or proteins with intrinsically disordered regions.

| S-EPMC7806674 | biostudies-literature

A decision tree model for the prediction of homodimer folding mechanism.

Project description:The formation of protein homodimer complexes for molecular catalysis and regulation is fascinating. The homodimer formation through 2S (2 state), 3SMI (3 state with monomer intermediate) and 3SDI (3 state with dimer intermediate) folding mechanism is known for 47 homodimer structures. Our dataset of forty-seven homodimers consists of twenty-eight 2S, twelve 3SMI and seven 3SDI. The dataset is characterized using monomer length, interface area and interface/total (I/T) residue ratio. It is found that 2S are often small in size with large I/T ratio and 3SDI are frequently large in size with small I/T ratio. Nonetheless, 3SMI have a mixture of these features. Hence, we used these parameters to develop a decision tree model. The decision tree model produced positive predictive values (PPV) of 72% for 2S, 58% for 3SMI and 57% for 3SDI in cross validation. Thus, the method finds application in assigning homodimers with folding mechanism.

| S-EPMC2859576 | biostudies-literature

Azospirillum: benefits that go far beyond biological nitrogen fixation.

Project description:The genus Azospirillum comprises plant-growth-promoting bacteria (PGPB), which have been broadly studied. The benefits to plants by inoculation with Azospirillum have been primarily attributed to its capacity to fix atmospheric nitrogen, but also to its capacity to synthesize phytohormones, in particular indole-3-acetic acid. Recently, an increasing number of studies has attributed an important role of Azospirillum in conferring to plants tolerance of abiotic and biotic stresses, which may be mediated by phytohormones acting as signaling molecules. Tolerance of biotic stresses is controlled by mechanisms of induced systemic resistance, mediated by increased levels of phytohormones in the jasmonic acid/ethylene pathway, independent of salicylic acid (SA), whereas in the systemic acquired resistance-a mechanism previously studied with phytopathogens-it is controlled by intermediate levels of SA. Both mechanisms are related to the NPR1 protein, acting as a co-activator in the induction of defense genes. Azospirillum can also promote plant growth by mechanisms of tolerance of abiotic stresses, named as induced systemic tolerance, mediated by antioxidants, osmotic adjustment, production of phytohormones, and defense strategies such as the expression of pathogenesis-related genes. The study of the mechanisms triggered by Azospirillum in plants can help in the search for more-sustainable agricultural practices and possibly reveal the use of PGPB as a major strategy to mitigate the effects of biotic and abiotic stresses on agricultural productivity.

| S-EPMC5935603 | biostudies-other

Temperature-dependent folding pathways of Pin1 WW domain: an all-atom molecular dynamics simulation of a Go model.

Project description:We study the folding thermodynamics and kinetics of the Pin1 WW domain, a three-stranded beta-sheet protein, by using all-atom (except nonpolar hydrogens) discontinuous molecular dynamics simulations at various temperatures with a Gō model. The protein exhibits a two-state folding kinetics near the folding transition temperature. A good agreement between our simulations and the experimental measurements by the Gruebele group has been found, and the simulation sheds new insights into the structure of transition state, which is hard to be straightforwardly captured in experiments. The simulation also reveals that the folding pathways at approximately the transition temperature and at low temperatures are much different, and an intermediate state at a low temperature is predicted. The transition state of this small beta-protein at its folding transition temperature has a well-established hairpin 1 made of beta1 and beta2 strands while its low-temperature kinetic intermediate has a formed hairpin 2 composed of beta2 and beta3 strands. Theoretical results are compared with other simulation results as well as available experimental data. This study confirms that specific side-chain packing in an all-atom Gō model can yield a reasonable prediction of specific folding kinetics for a given protein. Different folding behaviors at different temperatures are interpreted in terms of the interplay of entropy and enthalpy in folding process.

| S-EPMC1959547 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data