Protein Structure along the Order–Disorder Continuum

Thermal fluctuations cause proteins to adopt an ensemble of conformations wherein the relative stability of the different ensemble members is determined by the topography of the underlying energy landscape. “Folded” proteins have relatively homogeneous ensembles, while “unfolded” proteins have heterogeneous ensembles. Hence, the labels “folded” and “unfolded” represent attempts to provide a qualitative characterization of the extent of structural heterogeneity within the underlying ensemble. In this work, we introduce an information-theoretic order parameter to quantify this conformational heterogeneity. We demonstrate that this order parameter can be estimated in a straightforward manner from an ensemble and is applicable to both unfolded and folded proteins. In addition, a simple formula for approximating the order parameter directly from crystallographic B factors is presented. By applying these metrics to a large sample of proteins, we show that proteins span the full range of the order–disorder axis.National Institutes of Health (U.S.) (NIH Grant 5R21NS063185-02

Understanding biomolecular motion, recognition, and allostery by use of conformational ensembles

We review the role conformational ensembles can play in the analysis of biomolecular dynamics, molecular recognition, and allostery. We introduce currently available methods for generating ensembles of biomolecules and illustrate their application with relevant examples from the literature. We show how, for binding, conformational ensembles provide a way of distinguishing the competing models of induced fit and conformational selection. For allostery we review the classic models and show how conformational ensembles can play a role in unravelling the intricate pathways of communication that enable allostery to occur. Finally, we discuss the limitations of conformational ensembles and highlight some potential applications for the future

Przedsiębiorczość i kreatywność jako narzędzia rozwiązywania problemów w bankowości i finansach

In this paper I analyze why is important to consider the entrepreneurship as a key tool for the bank crisis. I related entrepreneurship with creativity, because both concepts are needed as you will see among its reading. The search investigation was based in a questionnaire to our students trying to discover their desire to become entrepreneurs and also I related the main characteristics of the entrepreneurship with the creativity ones. Why did I do that? Because, at the present moment, the banks need other kind of management, other styles and the young people, I mean, the future students could help to reach it.W niniejszym artykule podjęto analizę roli przedsiębiorczości jako narzędzia wspierającego minimalizację kryzysu bankowego. W pracy analizowano przedsiębiorczość i oraz aspekty związane z kreatywnością. Badanie oparto na kwestionariuszu ankiety. Respondentem była grupa studentów wykazujących predyspozycje przedsiębiorcze oraz kreatywność. Z jakiego powodu tak się stało? Ponieważ, w chwili obecnej banki potrzebują innego rodzaju i stylu zarządzania, zaś odpowiednio ukierunkowana i o pewnych predyspozycjach młodzież pomoże te cele osiągnąć

Metabolic rewiring of the hypertensive kidney

Hypertension is a persistent epidemic across the developed world that is closely associated with kidney disease. Here, we applied a metabolomic, phosphoproteomic, and proteomic strategy to analyze the effect of hypertensive insults on kidneys.Our data revealed the metabolic aspects of hypertension-induced glomerular sclerosis, including lipid breakdown at early disease stages and activation of anaplerotic pathways to regenerate energy equivalents to counter stress. For example, branched-chain amino acids and proline, required for collagen synthesis, were depleted in glomeruli at early time points. Furthermore, indicators of metabolic stress were reflected by low amounts of ATP and NADH and an increased abundance of oxidized lipids derived from lipid breakdown. These processes were specific to kidney glomeruli where metabolic signaling occurred through mTOR and AMPK signaling. Quantitative phosphoproteomics combined with computational modeling suggested that these processes controlled key molecules in glomeruli and specifically podocytes, including cytoskeletal components and GTP-binding proteins, which would be expected to compete for decreasing amounts of GTP at early time points. As a result, glomeruli showed increased expression of metabolic enzymes of central carbon metabolism, amino acid degradation, and lipid oxidation, findings observed in previously published studies from other disease models and patients with glomerular damage. Overall, multilayered omics provides an overview of hypertensive kidney damage and suggests that metabolic or dietary interventions could prevent and treat glomerular disease and hypertension-induced nephropathy