scholarly journals Functional determinants of protein assembly into homomeric complexes

2016 ◽  
Author(s):  
L. Therese Bergendahl ◽  
Joseph A. Marsh
Keyword(s):  
Conformational Changes ◽  
Protein Function ◽  
Quaternary Structure ◽  
Systematic Analysis ◽  
Functional Annotations ◽  
Evolutionary Selection ◽  
Large Numbers ◽  
Different Types ◽  
And Function ◽  
The Relationship

AbstractApproximately half of proteins with experimentally determined structures can interact with other copies of themselves and assemble into homomeric complexes, the overwhelming majority of which (>96%) are symmetric. Although homomerisation is often assumed to be functionally beneficial and the result of evolutionary selection, there has been little systematic analysis of the relationship between homomer structure and function. Here, utilizing the large numbers of structures and functional annotations now available, we have investigated how proteins that assemble into different types of homomers are associated with different biological functions. We observe that homomers from different symmetry groups are significantly enriched in distinct functions, and can often provide simple physical and geometrical explanations for these associations in regards to substrate recognition or physical environment. One of the strongest associations is the tendency for metabolic enzymes to form dihedral complexes, which we suggest is closely related to allosteric regulation. We provide a physical explanation for why allostery is related to dihedral complexes: it allows for efficient propagation of conformational changes across isologous (i.e. symmetric) interfaces. Overall we demonstrate a clear relationship between protein function and homomer symmetry that has important implications for understanding protein evolution, as well as for predicting protein function and quaternary structure.

scholarly journals CoDNaS-RNA: a database of Conformational Diversity in the Native State of RNA

2020 ◽  
Author(s):  
Martín González Buitrón ◽  
Ronaldo Romario Tunque Cahui ◽  
Emilio García Ríos ◽  
Layla Hirsh ◽  
María Silvina Fornasari ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Structural Features ◽  
Rna Structures ◽  
Rna Molecules ◽  
Functional Annotations ◽  
Public Resource ◽  
Conformational Diversity ◽  
Dynamics And Function ◽  
And Function ◽  
The Relationship

AbstractConformational changes in RNA native ensembles are central to fulfill many of their biological roles. Systematic knowledge of the extent and possible modulators of this conformational diversity is desirable to better understand the relationship between RNA dynamics and function.We have developed CoDNaS-RNA as the first database of conformational diversity in RNA molecules. Known RNA structures are retrieved and clustered to identify alternative conformers of each molecule. Pairwise structural comparisons within each cluster allows to measure the variability of the molecule. Additional data on structural features, molecular interactions and functional annotations are provided. CoDNaS-RNA is implemented as a public resource that can be of much interest for computational and bench scientists alike.AvailabilityCoDNaS-RNA is freely accessible at http://ufq.unq.edu.ar/[email protected]

scholarly journals A Novel Method for Functional Annotation Prediction Based on Combination of Classification Methods

2014 ◽  
Vol 2014 ◽  
pp. 1-9
Author(s):  
Jaehee Jung ◽  
Heung Ki Lee ◽  
Gangman Yi
Keyword(s):  
Protein Function ◽  
Protein Function Prediction ◽  
Controlled Vocabulary ◽  
Functional Annotations ◽  
Functional Homology ◽  
Large Sets ◽  
Unknown Protein ◽  
Protein Functions ◽  
Novel Method ◽  
The Relationship

Automated protein function prediction defines the designation of functions of unknown protein functions by using computational methods. This technique is useful to automatically assign gene functional annotations for undefined sequences in next generation genome analysis (NGS). NGS is a popular research method since high-throughput technologies such as DNA sequencing and microarrays have created large sets of genes. These huge sequences have greatly increased the need for analysis. Previous research has been based on the similarities of sequences as this is strongly related to the functional homology. However, this study aimed to designate protein functions by automatically predicting the function of the genome by utilizing InterPro (IPR), which can represent the properties of the protein family and groups of the protein function. Moreover, we used gene ontology (GO), which is the controlled vocabulary used to comprehensively describe the protein function. To define the relationship between IPR and GO terms, three pattern recognition techniques have been employed under different conditions, such as feature selection and weighted value, instead of a binary one.

scholarly journals NCIPLOT4: A New Step Towards a Fast Quantification of Noncovalent Interactions

2019 ◽  
Author(s):  
Roberto Boto ◽  
Francesca Peccati ◽  
Rubén Laplaza ◽  
chaoyu quan ◽  
Alessandra Carbone ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Driving Forces ◽  
Noncovalent Interactions ◽  
Noncovalent Interaction ◽  
Simple Approach ◽  
Machine Learning Algorithms ◽  
Definition Of ◽  
And Function ◽  
The Relationship

<br>The quantification of noncovalent interactions in big systems is of crucial importance for understanding the structure and function of biosystems. The NCI method [J. Am. Chem. Soc. 132 , 6498 (2010)] enables to identify attractive and repulsive noncovalent interactions from promolecular densities in a fast manner. However, the approach remained up to now visual/qualitative, the relationship with energetics was conspicuously missing. We present a new version of NCIPLOT which allows quantifying the properties of the NonCovalent Interaction (NCI) regions in a fast manner. In order to do so, the definition of NCI volumes is introduced, which allows quantification of intra and intermolecular NCI properties in big systems where wavefunctions are not available. The connection between these integrals and energetics is reviewed for benchmark systems (S66 8), showing that our simple approach can lead to GGAquality energies while scaling with the number of atoms involved in the interaction (not the total number of atoms). The new implementation also includes an adaptive grid which allows the computation in a fast, parallelizable and efficient computational environment. The relationship with energetics derived from force fields is highlighted<br>and the faster algorithm exploited to analyze the evolution of interactions along MD trajectories. Through machine learning algorithms we characterize the relevance of NCI integrals in understanding the energetics of big systems, which is then applied in revealing the energetic changes along conformational changes, as well as identifying the atoms involved. This simple approach enables to identify the driving forces in biomolecular structural changes both at the spatial and energetic levels, while going beyond a mere parametrized-distances analysis.<br>

scholarly journals Crosstalk Between Tumor-Associated Microglia/Macrophages and CD8-Positive T Cells Plays a Key Role in Glioblastoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng Tu ◽  
Xu Lin ◽  
Jili Qiu ◽  
Jiaqi Zhou ◽  
Hui Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Malignant Disease ◽  
Immune Therapy ◽  
Cell Types ◽  
Different Types ◽  
The Central Nervous System ◽  
And Function ◽  
The Relationship

Glioblastoma is considered to be the most malignant disease of the central nervous system, and it is often associated with poor survival. The immune microenvironment plays a key role in the development and treatment of glioblastoma. Among the different types of immune cells, tumor-associated microglia/macrophages (TAM/Ms) and CD8-positive (CD8+) T cells are the predominant immune cells, as well as the most active ones. Current studies have suggested that interaction between TAM/Ms and CD8+ T cells have numerous potential targets that will allow them to overcome malignancy in glioblastoma. In this review, we summarize the mechanism and function of TAM/Ms and CD8+ T cells involved in glioblastoma, as well as update on the relationship and crosstalk between these two cell types, to determine whether this association alters the immune status during glioblastoma development and affects optimal treatment. We focus on the molecular factors that are crucial to this interaction, and the role that this crosstalk plays in the biological processes underlying glioblastoma treatment, particularly with regard to immune therapy. We also discuss novel therapeutic targets that can aid in resolving reticular connections between TAM/Ms and CD8+ T cells, including depletion and reprogramming TAM/Ms and novel TAM/Ms-CD8+ T cell cofactors with potential translational usage. In addition, we highlight the challenges and discuss future perspectives of this crosstalk between TAM/Ms and CD8+ T cells.

NCIPLOT4: A New Step Towards a Fast Quantification of Noncovalent Interactions

2020 ◽  
Author(s):  
Roberto Boto ◽  
Francesca Peccati ◽  
Rubén Laplaza ◽  
chaoyu quan ◽  
Alessandra Carbone ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Driving Forces ◽  
Noncovalent Interactions ◽  
Noncovalent Interaction ◽  
Simple Approach ◽  
Machine Learning Algorithms ◽  
Definition Of ◽  
And Function ◽  
The Relationship

<br>The quantification of noncovalent interactions in big systems is of crucial importance for understanding the structure and function of biosystems. The NCI method [J. Am. Chem. Soc. 132 , 6498 (2010)] enables to identify attractive and repulsive noncovalent interactions from promolecular densities in a fast manner. However, the approach remained up to now visual/qualitative, the relationship with energetics was conspicuously missing. We present a new version of NCIPLOT which allows quantifying the properties of the NonCovalent Interaction (NCI) regions in a fast manner. In order to do so, the definition of NCI volumes is introduced, which allows quantification of intra and intermolecular NCI properties in big systems where wavefunctions are not available. The connection between these integrals and energetics is reviewed for benchmark systems (S66 8), showing that our simple approach can lead to GGAquality energies while scaling with the number of atoms involved in the interaction (not the total number of atoms). The new implementation also includes an adaptive grid which allows the computation in a fast, parallelizable and efficient computational environment. The relationship with energetics derived from force fields is highlighted<br>and the faster algorithm exploited to analyze the evolution of interactions along MD trajectories. Through machine learning algorithms we characterize the relevance of NCI integrals in understanding the energetics of big systems, which is then applied in revealing the energetic changes along conformational changes, as well as identifying the atoms involved. This simple approach enables to identify the driving forces in biomolecular structural changes both at the spatial and energetic levels, while going beyond a mere parametrized-distances analysis.<br>

scholarly journals The importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Renata Fioravanti Tarabini ◽  
Luís Fernando Saraiva Macedo Timmers ◽  
Carlos Eduardo Sequeiros-Borja ◽  
Osmar Norberto de Souza
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Conformational Changes ◽  
Protein Function ◽  
Environmental Changes ◽  
Quaternary Structure ◽  
Single Point ◽  
Point Mutations ◽  
Conformational Ensembles ◽  
Dynamics Simulations ◽  
Coa Reductase

Abstract Flexibility is a feature intimately related to protein function, since conformational changes can be used to describe environmental changes, chemical modifications, protein-protein and protein-ligand interactions. In this study, we have investigated the influence of the quaternary structure of 2-trans-enoyl-ACP (CoA) reductase or InhA, from Mycobacterium tuberculosis, to its flexibility. We carried out classical molecular dynamics simulations using monomeric and tetrameric forms to elucidate the enzyme’s flexibility. Overall, we observed statistically significant differences between conformational ensembles of tertiary and quaternary structures. In addition, the enzyme’s binding site is the most affected region, reinforcing the importance of the quaternary structure to evaluate the binding affinity of small molecules, as well as the effect of single point mutations to InhA protein dynamics.

scholarly journals Native proteins trap high-energy transit conformations

2015 ◽  
Vol 1 (9) ◽  
pp. e1501188 ◽  
Author(s):  
Andrew E. Brereton ◽  
P. Andrew Karplus
Keyword(s):  
Protein Folding ◽  
Conformational Changes ◽  
Protein Function ◽  
Protein Structures ◽  
High Energy ◽  
Native Proteins ◽  
Regulate Protein ◽  
The Right ◽  
And Function ◽  
Open Question

During protein folding and as part of some conformational changes that regulate protein function, the polypeptide chain must traverse high-energy barriers that separate the commonly adopted low-energy conformations. How distortions in peptide geometry allow these barrier-crossing transitions is a fundamental open question. One such important transition involves the movement of a non-glycine residue between the left side of the Ramachandran plot (that is, ϕ < 0°) and the right side (that is, ϕ > 0°). We report that high-energy conformations with ϕ ~ 0°, normally expected to occur only as fleeting transition states, are stably trapped in certain highly resolved native protein structures and that an analysis of these residues provides a detailed, experimentally derived map of the bond angle distortions taking place along the transition path. This unanticipated information lays to rest any uncertainty about whether such transitions are possible and how they occur, and in doing so lays a firm foundation for theoretical studies to better understand the transitions between basins that have been little studied but are integrally involved in protein folding and function. Also, the context of one such residue shows that even a designed highly stable protein can harbor substantial unfavorable interactions.

scholarly journals CoRINs: A tool to compare residue interaction networks from homologous proteins and conformers

2020 ◽  
Author(s):  
Felipe V. da Fonseca ◽  
Romildo O. Souza Júnior ◽  
Marília V. A. de Almeida ◽  
Thiago D. Soares ◽  
Diego A. A. Morais ◽  
...  
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Conformational Changes ◽  
Protein Function ◽  
Protein Structures ◽  
Software Tool ◽  
Interaction Networks ◽  
Homologous Proteins ◽  
Residue Interaction ◽  
And Function

ABSTRACTMotivationA useful approach to evaluate protein structure and quickly visualize crucial physicochemical interactions related to protein function is to construct Residue Interactions Networks (RINs). By using this application of graphs theory, the amino acid residues constitute the nodes, and the edges represent their interactions with other structural elements. Although several tools that construct RINs are available, many of them do not compare RINs from distinct protein structures. This comparison can give valuable insights into the understanding of conformational changes and the effects of amino acid substitutions in protein structure and function. With that in mind, we present CoRINs (Comparator of Residue Interaction Networks), a software tool that extensively compares RINs. The program has an accessible and user-friendly web interface, which summarizes the differences in several network parameters using interactive plots and tables. As a usage example of CoRINs, we compared RINs from conformers of two cancer-associated proteins.AvailabilityThe program is available at https://github.com/LasisUFRN/CoRINs.

scholarly journals Protein dynamics and function from solution state NMR spectroscopy

2016 ◽  
Vol 49 ◽  
Author(s):  
Michael Kovermann ◽  
Per Rogne ◽  
Magnus Wolf-Watz
Keyword(s):  
Nmr Spectroscopy ◽  
Protein Dynamics ◽  
Conformational Changes ◽  
Protein Function ◽  
Time Intervals ◽  
Energy Landscape Theory ◽  
Nmr Techniques ◽  
Dynamics And Function ◽  
And Function ◽  
Design Experiments

AbstractIt is well-established that dynamics are central to protein function; their importance is implicitly acknowledged in the principles of the Monod, Wyman and Changeux model of binding cooperativity, which was originally proposed in 1965. Nowadays the concept of protein dynamics is formulated in terms of the energy landscape theory, which can be used to understand protein folding and conformational changes in proteins. Because protein dynamics are so important, a key to understanding protein function at the molecular level is to design experiments that allow their quantitative analysis. Nuclear magnetic resonance (NMR) spectroscopy is uniquely suited for this purpose because major advances in theory, hardware, and experimental methods have made it possible to characterize protein dynamics at an unprecedented level of detail. Unique features of NMR include the ability to quantify dynamics (i) under equilibrium conditions without external perturbations, (ii) using many probes simultaneously, and (iii) over large time intervals. Here we review NMR techniques for quantifying protein dynamics on fast (ps-ns), slow (μs-ms), and very slow (s-min) time scales. These techniques are discussed with reference to some major discoveries in protein science that have been made possible by NMR spectroscopy.

scholarly journals Conflicting notions of language in metalinguistic discourses in Lithuania, Norway and Serbia

2015 ◽  
pp. 1-32
Author(s):  
Vuk Vukotić
Keyword(s):  
Personal Identity ◽  
Language Ideology ◽  
Language Ideologies ◽  
Online News ◽  
Identity Change ◽  
Different Types ◽  
The Difference ◽  
And Function ◽  
The Relationship ◽  
Standard Language Ideology

The article analyses the notions of language and their elements in metalinguistic comments taken from comment sections in online news portals from Lithuania, Norway and Serbia. The aim is to find and categorize different types of language notions. The goals were to analyse the elements of the notions of language and categorize them according to the metaphors found in the discourse. The empirical data was taken from comments under three news (three for each country), approximately 1640 comments were collected and the ones that contained metaphorical representations of language were analysed, 257 in total. The results show eight different notions of language, which are called: prescriptivist / authoritarian, instrumentalist, ethnolinguistic, communicative, essentialist, „personal identity“, elitist and constructivist. The last three notions are specific for only one of the environments and are discussed in greater detail. From the users’ perspective, the difference between the notions is based on several elements, most importantly: the place of language in society (what is the relationship to standard and non-standard varieties) perception of change and function and functionality of language. The results also show that notions of ‘pure language’ are connected not only to the ethnolinguistic notion of language (language as a part of the identity, change is understood as decay), but also with other varieties of language are connected with different (even opposing) ideals and practical concerns (language as a neutral tool of communication, as a separate organism, substance etc.), and, finally, those notions of language, where the differentiation between the varieties of language is not important, is only connected with the communicative function (communicative notion of language – language is communication). Speaking about language ideologies in general, results show that there are of language in which standard language ideology (according to Milroy 2001) is negatively valued.

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