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>

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>

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>

Influence of Ascorbic Acid on the Structure and Function of Alpha-2- macroglobulin: Investigations using Spectroscopic and Thermodynamic Techniques

2020 ◽  
Vol 27 (3) ◽  
pp. 201-209
Author(s):  
Syed Saqib Ali ◽  
Mohammad Khalid Zia ◽  
Tooba Siddiqui ◽  
Haseeb Ahsan ◽  
Fahim Halim Khan
Keyword(s):  
Ascorbic Acid ◽  
Conformational Changes ◽  
Structural Changes ◽  
The Body ◽  
Titration Calorimetry ◽  
Spectroscopic Techniques ◽  
Human Beings ◽  
Plasma Ascorbic Acid ◽  
Dietary Antioxidant ◽  
And Function

Background: Ascorbic acid is a classic dietary antioxidant which plays an important role in the body of human beings. It is commonly found in various foods as well as taken as dietary supplement. Objective: The plasma ascorbic acid concentration may range from low, as in chronic or acute oxidative stress to high if delivered intravenously during cancer treatment. Sheep alpha-2- macroglobulin (α2M), a human α2M homologue is a large tetrameric glycoprotein of 630 kDa with antiproteinase activity, found in sheep’s blood. Methods: In the present study, the interaction of ascorbic acid with alpha-2-macroglobulin was explored in the presence of visible light by utilizing various spectroscopic techniques and isothermal titration calorimetry (ITC). Results: UV-vis and fluorescence spectroscopy suggests the formation of a complex between ascorbic acid and α2M apparent by increased absorbance and decreased fluorescence. Secondary structural changes in the α2M were investigated by CD and FT-IR spectroscopy. Our findings suggest the induction of subtle conformational changes in α2M induced by ascorbic acid. Thermodynamics signatures of ascorbic acid and α2M interaction indicate that the binding is an enthalpy-driven process. Conclusion: It is possible that ascorbic acid binds and compromises antiproteinase activity of α2M by inducing changes in the secondary structure of the protein.

Physicianship and the Rebirth of Medical Education

2018 ◽  
Author(s):  
J. Donald Boudreau ◽  
Eric Cassell ◽  
Abraham Fuks
Keyword(s):  
Medical Education ◽  
Educational Process ◽  
Medical Attention ◽  
Patient Centeredness ◽  
Goals Of Medicine ◽  
The Subject ◽  
Definition Of ◽  
And Function ◽  
William Osler ◽  
The Relationship

This book reimagines medical education and reconstructs its design. It originates from a reappraisal of the goals of medicine and the nature of the relationship between doctor and patient. The educational blueprint outlined is called the “Physicianship Curriculum” and rests on two linchpins. First is a new definition of sickness: Patients know themselves to be ill when they cannot pursue their purposes and goals in life because of impairments in functioning. This perspective represents a bulwark against medical attention shifting from patients to diseases. The curriculum teaches about patients as functional persons, from their anatomy to their social selves, starting in the first days of the educational program and continuing throughout. Their teaching also rests on the rock-solid grounding of medicine in the sciences and scientific understandings of disease and function. The illness definition and knowledge base together create a foundation for authentic patient-centeredness. Second, the training of physicians depends on and culminates in development of a unique professional identity. This is grounded in the historical evolution of the profession, reaching back to Hippocrates. It leads to reformulation of the educational process as clinical apprenticeships and moral mentorships. “Rebirth” in the title suggests that critical ingredients of medical education have previously been articulated. The book argues that the apprenticeship model, as experienced, enriched, taught, and exemplified by William Osler, constitutes a time-honored foundation. Osler’s “natural method of teaching the subject of medicine” is a precursor to the Physicianship Curriculum.

scholarly journals Insight to Functional Conformation and Noncovalent Interactions of Protein-Protein Assembly Using MALDI Mass Spectrometry

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4979
Author(s):  
Marco Giampà ◽  
Elvira Sgobba
Keyword(s):  
Mass Spectrometry ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Noncovalent Interactions ◽  
Conformational Dynamics ◽  
High Sensitivity ◽  
Maldi Mass Spectrometry ◽  
Noncovalent Interaction ◽  
Ionization Mass ◽  
Label Free

Noncovalent interactions are the keys to the structural organization of biomolecule e.g., proteins, glycans, lipids in the process of molecular recognition processes e.g., enzyme-substrate, antigen-antibody. Protein interactions lead to conformational changes, which dictate the functionality of that protein-protein complex. Besides biophysics techniques, noncovalent interaction and conformational dynamics, can be studied via mass spectrometry (MS), which represents a powerful tool, due to its low sample consumption, high sensitivity, and label-free sample. In this review, the focus will be placed on Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) and its role in the analysis of protein-protein noncovalent assemblies exploring the relationship within noncovalent interaction, conformation, and biological function.

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 Depression as a symptom of cerebrovascular diseases: A review.

2021 ◽  
Author(s):  
Nurtai Abykayev ◽  
Marat Kulmanov ◽  
Arman Lurye ◽  
Dinara Zhumanbayeva
Keyword(s):  
Structural Changes ◽  
Depressive Disorders ◽  
Cognitive Change ◽  
Cerebrovascular Diseases ◽  
Brain Diseases ◽  
Prodromal Symptom ◽  
Pubmed Database ◽  
Inflammatory Processes ◽  
Definition Of ◽  
The Relationship

Abstract Depression can be prodromal symptom of brain diseases, but this association remains poorly studied with regards to cerebrovascular diseases. The aim of this review was to analyze the relationship between cerebrovascular diseases and depression. The objectives of the current review were: 1 – to assess the relationship between structural changes in brain and depression; 2 – to evaluate the connection between cognitive performance and cerebrovascular impairment; 3 – to assess the relationship between biological correlates of brain diseases and depression. A search of PubMed database was conducted focusing on papers published until 4th March, 2021. The following terms were used: brain diseases and depression/pathology. A depressive disorder might have relationship with structural or biological changes in the brain. However, this does not give the precise conclusion that depression definitely appears while person has cerebrovascular disease. Nevertheless, people with cerebrovascular diseases were observed to have high depression scales scores, while depression and cerebrovascular diseases had inflammation, cognitive change, or dopamine and serotonin changes in common. This is an overall limit concerning the definition of depression and cerebrovascular diseases. So, in this review we observed all the possible connections between depression and brain diseases. Depression seems to be associated with cerebrovascular changes in people. They might have structural changes in hippocampus, white matter, cortex and other parts, as well as inflammatory processes, neuromediators changes, and cognitive decline. Thus, it is essential to evaluate depressive disorders in people with brain diseases as precisely as possible.

scholarly journals Factors Influence Development of Village Libraries

2021 ◽  
Vol 7 (2) ◽  
pp. 200-214
Author(s):  
Ella Erliyana
Keyword(s):  
Human Resources ◽  
Driving Forces ◽  
Public Library ◽  
Snowball Sampling ◽  
Use Of Technology ◽  
Strategic Role ◽  
And Function ◽  
The Village ◽  
The Relationship ◽  
Descriptive Qualitative

Background of the study: The village library is an interesting type of public library for research studies. The uniqueness of the village library lies in the role and function that is close to the life of the community in the village. The village library has a strategic role in developing human resources in the village. Purpose: The purpose of this study is to describe the factors that influence the development of village libraries in the Sleman Regency. The purpose of the next research is to discuss the relationship between the factors that are the driving forces and inhibitors of libraries in managing village libraries. Method: The approach method in this research uses descriptive qualitative. Descriptive qualitative research in which the researcher draws and extracts information from the phenomenon of village library development factors. The research location is in the village library in Sleman Regency. The informant selection technique uses snowball sampling as the main informant, which is then supplemented with proposive sampling. Findings: The results found internal factors that influence the development of the village library organization, among others, support of human resources, the formation of organizational structure, commitment from various stakeholders, internal and external regulations, allocation of funding for routine libraries, the use of technology, collaboration and networks built together with government and non-government institutions, the ability to analyze the needs of the community and innovation in dealing with the challenges of the village library, the relationship between these factors can support the success of the administration and management of the village library. Conclusion: Studies in village libraries in Sleman Regency show that there are village libraries that are capable of making changes (transformation), but there are also libraries that are not yet capable of transforming libraries.

scholarly journals Does Covera-19 know ‘when to hold ‘em or ‘when to fold ‘em? A translational thought experiment

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Gerald Dieter Griffin
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Structural Integrity ◽  
Thought Experiment ◽  
Amino Acid Sequences ◽  
Acid And Base ◽  
Effects Of Ph ◽  
Base Balance ◽  
Environmental Milieu ◽  
And Function

AbstractThe function of proteins depends on their structure. The structural integrity of proteins is dynamic and depends on interacting nearby neighboring moieties that influence their properties and induce folding and structural changes. The conformational changes induced by these nearby neighbors in the micro-environmental milieu at that moment are guided by chemical or electrical bonding attractions.There are few literature references that describe the potential for environmental milieu changes to disfavor SARS-CoV-2 attachment to a receptor for survival outside of a host. There are many studies on the effects of pH (acid and base balance) supporting its importance for protein structure and function, but few focus on pH role in extracellular or intracellular protein or actionable requirements of Covera-19.‘Fold ‘em or Hold ‘em’ is seen by the various functions and effects of furin as it seeks an acidic milieu for action or compatible amino acid sequences which is currently aided by its histidine component and the structural changes of proteins as they enter or exit the host. Questions throughout the text are posed to focus on current thoughts as reviewing applicable COVID-19 translational research science in order to understand the complexities of Covid-19.The pH needs of COVID-19 players and its journey through the human host and environment as well as some efficacious readily available repurposed drugs and out-of-the box and easily available treatments are reviewed.

scholarly journals Molecular Dynamics of SARS-CoV-2 Nsp1 Structural Changes Associated with Variant Mutations

2021 ◽  
Author(s):  
Shokouh Rezaei ◽  
Yahya Sefidbakht ◽  
Filipe Pereira
Keyword(s):  
Molecular Dynamics ◽  
Conformational Changes ◽  
Structural Changes ◽  
Structure And Function ◽  
Dynamics Simulation ◽  
Structural Protein ◽  
Wild Type ◽  
Deletion Mutations ◽  
And Function

Abstract SARS-CoV-2 non-structural protein 1 (Nsp1) is a virulence factor that inhibits the translation of host mRNAs and interact with viral RNA. Despite the relevance of Nsp1, few studies have been conducted to understand the effect of mutations on Nsp1 structure and function. Here, we provide a molecular dynamics simulation of SARS-CoV-2 Nsp1, wild type and variants. We found that SARS-CoV-2 Nsp1 has a more Rg value than SARS-CoV-1 Nsp1, with indicate an effect on the folding protein. This result suggest that SARS-CoV-2 Nsp1 can more easily approach the active site of the ribosome compared to SARS-CoV-1 Nsp1. In addition, we found that the C-terminal of the SARS-CoV-2 Nsp1, in particular residues 164 to 170, are more flexible than other regions of SARS-CoV-2 Nsp1 and SARS-CoV-1 Nsp1, confirming the role of this region in the interaction with the 40S subunit. Moreover, multiple deletion mutations have been found in the N/C-terminal of the SARS-CoV-2 Nsp1, which seems the effect of SARS-CoV-2 Nsp1 multiple deletions is greater than that of substitutions. Among all deletions, D156-158 and D80-90 may destabilize the protein structure and possibly increase the virulence of the SARS-CoV-2. Overall, our findings reinforce the importance of studying Nsp1 conformational changes in new variants and its effect on virulence of SARS-CoV-2.

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