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HCA Healthcare Journal of Medicine 2023Description Our EMRs should empower us, but unfortunately, they often bully and frustrate us. This poem is an expression of my frustration and disappointment with my own...
Description Our EMRs should empower us, but unfortunately, they often bully and frustrate us. This poem is an expression of my frustration and disappointment with my own EMR. Creating it allowed me to channel my frustration and disappointment.
PubMed: 37434907
DOI: 10.36518/2689-0216.1581 -
Accounts of Chemical Research Mar 2021Are all protein interactions fully optimized? Do suboptimal interactions compromise specificity? What is the functional impact of frustration? Why does evolution not... (Review)
Review
Are all protein interactions fully optimized? Do suboptimal interactions compromise specificity? What is the functional impact of frustration? Why does evolution not optimize some contacts? Proteins and their complexes are best described as ensembles of states populating an energy landscape. These ensembles vary in breadth from narrow ensembles clustered around a single average X-ray structure to broader ensembles encompassing a few different functional "taxonomic" states on to near continua of rapidly interconverting conformations, which are called "fuzzy" or even "intrinsically disordered". Here we aim to provide a comprehensive framework for confronting the structural and dynamical continuum of protein assemblies by combining the concepts of energetic frustration and interaction fuzziness. The diversity of the protein structural ensemble arises from the frustrated conflicts between the interactions that create the energy landscape. When frustration is minimal after folding, it results in a narrow ensemble, but residual frustrated interactions result in fuzzy ensembles, and this fuzziness allows a versatile repertoire of biological interactions. Here we discuss how fuzziness and frustration play off each other as proteins fold and assemble, viewing their significance from energetic, functional, and evolutionary perspectives.We demonstrate, in particular, that the common physical origin of both concepts is related to the ruggedness of the energy landscapes, intramolecular in the case of frustration and intermolecular in the case of fuzziness. Within this framework, we show that alternative sets of suboptimal contacts may encode specificity without achieving a single structural optimum. Thus, we demonstrate that structured complexes may not be optimized, and energetic frustration is realized via different sets of contacts leading to multiplicity of specific complexes. Furthermore, we propose that these suboptimal, frustrated, or fuzzy interactions are under evolutionary selection and expand the biological repertoire by providing a multiplicity of biological activities. In accord, we show that non-native interactions in folding or interaction landscapes can cooperate to generate diverse functional states, which are essential to facilitate adaptation to different cellular conditions. Thus, we propose that not fully optimized structures may actually be beneficial for biological activities of proteins via an alternative set of suboptimal interactions. The importance of such variability has not been recognized across different areas of biology.This account provides a modern view on folding, function, and assembly across the protein universe. The physical framework presented here is applicable to the structure and dynamics continuum of proteins and opens up new perspectives for drug design involving not fully structured, highly dynamic protein assemblies.
Topics: Crystallography, X-Ray; Models, Molecular; Protein Conformation; Protein Folding; Proteins
PubMed: 33550810
DOI: 10.1021/acs.accounts.0c00813 -
Journal of Molecular Biology Feb 2023Proteins interact with other proteins, with nucleic acids, lipids, carbohydrates and various small molecules in the living cell. These interactions have been quantified... (Review)
Review
Proteins interact with other proteins, with nucleic acids, lipids, carbohydrates and various small molecules in the living cell. These interactions have been quantified and structurally characterized in numerous studies such that we today have a comprehensive picture of protein structure and function. However, proteins are dynamic and even folded proteins are likely more heterogeneous than they appear in most descriptions. One property of proteins that relies on dynamics and heterogeneity is allostery, the ability of a protein to change structure and function upon ligand binding to an allosteric site. Over the last decades the concept of allostery was broadened to embrace all types of long-range interactions across a protein including purely entropic changes without a conformational change in single protein domains. But with this re-definition came a problem: How do we measure allostery? In this opinion, we discuss some caveats arising from the quantitative description of single-domain allostery from an experimental perspective and how the limitations cannot be separated from the definition of allostery per se. Furthermore, we attempt to tie together allostery with the concept of frustration in an effort to investigate the links between these two complex, and yet general, properties of proteins. We arrive at the conclusion that the sensitivity to perturbation of allosteric networks in single protein domains is too large for the networks to be of significant biological relevance.
Topics: Allosteric Regulation; Proteins; Allosteric Site; Entropy; Protein Domains
PubMed: 36586463
DOI: 10.1016/j.jmb.2022.167934 -
Scientific Reports Jan 2021Fluctuations in health and sleep are common, but we know surprisingly little about how these daily life stressors affect one's level of frustration and sensitivity to...
Fluctuations in health and sleep are common, but we know surprisingly little about how these daily life stressors affect one's level of frustration and sensitivity to becoming frustrated. In this pre-registered study, 517 participants (M = 30.4, SD = 10.4) reported their current sickness symptoms, health status, sleepiness, and sleep duration and quality the previous night. They also rated their general frustration and mood before and after a mild frustration-eliciting task. In the task, participants were instructed to copy geometric shapes onto a piece of paper, without lifting the pen from the paper. Participants were given three minutes to copy the eight shapes, but in order to induce frustration half of them were unsolvable. The study was subsequently repeated in an independent sample (N = 113). Frustration increased in response to the task; however, those with the worst sickness symptoms or sleep health reduced or did not change their frustration levels. Instead, across both studies, frustration was already high at baseline for these individuals. These findings indicate that being sick or having poor sleep is related to high general frustration, but resilience to further frustration due to mild frustrating situations.
Topics: Adult; Affect; Disease; Female; Frustration; Health; Humans; Male; Sleep
PubMed: 33452313
DOI: 10.1038/s41598-020-80461-4 -
Journal of General Internal Medicine Jan 2022
Topics: Chronic Pain; Decision Making; Decision Making, Shared; Frustration; Humans; Patient Participation; Primary Health Care
PubMed: 34173195
DOI: 10.1007/s11606-021-06967-3 -
The Liverpool Law Review 2022One of the key legal questions that COVID-19 has raised relates to the status of the traditional contractual doctrine of frustration. The pandemic and the ongoing...
One of the key legal questions that COVID-19 has raised relates to the status of the traditional contractual doctrine of frustration. The pandemic and the ongoing lockdowns across the globe have made it difficult for many contracts to perform. At the same time, there is a deep doctrinal and conceptual confusion with respect to the very essentials of this doctrine and its remedy - i.e., what happens after an adjudicative tribunal declares that a given contract has been frustrated. The paper offers a unified conceptual account of the frustration doctrine and claims that both the doctrine and its remedy crystallize a single unifying idea.
PubMed: 35757386
DOI: 10.1007/s10991-022-09305-7 -
International Journal of Environmental... Jun 2020Sports research has been focused on the assessment of basic needs satisfaction, considering its absence as a representation of needs frustration. However, recent...
Sports research has been focused on the assessment of basic needs satisfaction, considering its absence as a representation of needs frustration. However, recent findings have suggested needs satisfaction and frustration as asymmetrical factors leading to differentiated outcomes. An accurate measurement of needs poses itself as a crucial aspect, facilitating coaches' understanding of athlete's motivational processes. This study aimed to examine the psychometric proprieties of the Basic Psychological Needs Satisfaction and Frustration Scale (BPNSFS) in a sample of Portuguese athletes. A multigroup analysis was conducted of gender, sport type, age, and years of sports practice. Additionally, needs satisfaction and needs frustration were tested as predictors of behavioral regulations examining the nomological validity of the BPNSFS. Data from 594 Portuguese athletes (38.6% female; M = 15.21; SD = 0.97) that represent two different sports (football and swimming) were analyzed. Confirmatory factor analysis and structural equation modeling procedures were followed to test the factor structure and nomological validity of the scale, respectively. Analyses indicated that the six-factor model provided an adequate fit (Comparative Fit Index = 0.947, Tucker-Lewis Index = 0.936, Standardized Root Mean Square = 0.039, Root Mean Square Error of Approximation = 0.048 (CI 90% = 0.043, 0.054)). Moreover, the multigroup analysis suggested invariance in the observed structure across groups. In addition, findings indicated a strong prediction between needs satisfaction and autonomous forms of motivation, whereas needs frustration predicted significantly controlled forms of motivation. The sport-adapted BPNSFS in a sample of Portuguese athletes seemed to be an adequate measure for the assessment of basic psychological needs satisfaction and frustration. Our findings suggested that this scale may be worth testing in future research in the sport context.
Topics: Adolescent; Athletes; Female; Frustration; Humans; Male; Motivation; Personal Autonomy; Personal Satisfaction
PubMed: 32517120
DOI: 10.3390/ijerph17114046 -
Journal of the American Chemical Society Mar 2022Long-range electron tunneling through metalloproteins is facilitated by evolutionary tuning of donor-acceptor electronic couplings, formal electrochemical potentials,...
Long-range electron tunneling through metalloproteins is facilitated by evolutionary tuning of donor-acceptor electronic couplings, formal electrochemical potentials, and active-site reorganization energies. Although the minimal frustration of the folding landscape enables this tuning, residual frustration in the vicinity of the metallocofactor can allow conformational fluctuations required for protein function. We show here that the constrained copper site in wild-type azurin is governed by an intricate pattern of minimally frustrated local and distant interactions that together enable rapid electron flow to and from the protein. In contrast, sluggish electron transfer reactions (unfavorable reorganization energies) of active-site azurin variants are attributable to increased frustration near to as well as distant from the copper site, along with an exaggerated oxidation-state dependence of both minimally and highly frustrated interaction patterns.
Topics: Azurin; Copper; Electron Transport; Electrons; Pseudomonas aeruginosa
PubMed: 35171591
DOI: 10.1021/jacs.1c13454 -
Haematologica Aug 2016
Topics: Antimetabolites, Antineoplastic; Biomarkers, Tumor; Clinical Trials as Topic; Frustration; Humans; Myelodysplastic Syndromes
PubMed: 27478197
DOI: 10.3324/haematol.2016.142836