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Bounded rationality

Joseph H Montoya, Andrew D Doyle, Jens K Nørskov, Aleksandra Vojvodic
The reactivity of solid oxide surfaces towards adsorption of oxygen and hydrogen is a key metric for the design of new catalysts for electrochemical water splitting. In this paper, we report on trends in the adsorption energy of different adsorbed intermediates derived from the oxidation and reduction of water for ternary ABO3 oxides in the cubic perovskite structure. Our findings support a previously reported trend that rationalizes the observed lower bound in oxygen evolution (OER) overpotentials from correlations in OH* and OOH* adsorption energies...
January 19, 2018: Physical Chemistry Chemical Physics: PCCP
Oliver McRae, Antoine Gaillard, James C Bird
When air is blown in a straw or tube near an air-liquid interface, typically one of two behaviors is observed: a dimple in the liquid's surface, or a frenzy of sputtering bubbles, waves, and spray. Here we report and characterize an intermediate regime that can develop when a confined air jet enters the interface at an angle. This regime is oscillatory with a distinct characteristic frequency and can develop periodic angled jets that can break up into monodisperse aerosols. The underlying mechanisms responsible for this highly periodic regime are not well understood...
July 2017: Physical Review. E
Márcio Santos Rocha, Ingeborg M Storm, Raniella Falchetto Bazoni, Ésio Bessa Ramos, Armando Hernandez-Garcia, Martien A Cohen Stuart, Frans Leermakers, Renko de Vries
As a model system to study the elasticity of bottle-brush polymers, we here introduce self-assembled DNA bottle brushes, consisting of a DNA main chain that can be very long and still of precisely defined length, and precisely monodisperse polypeptide side chains that are physically bound to the DNA main chains. Polypeptide side chains have a diblock architecture, where one block is a small archaeal nucleoid protein Sso7d that strongly binds to DNA. The other block is a net neutral, hydrophilic random coil polypeptide with a length of exactly 798 amino acids...
January 9, 2018: Macromolecules
Ravi Kumar Verma, Ara M Abramyan, Mayako Michino, R Benjamin Free, David R Sibley, Jonathan A Javitch, J Robert Lane, Lei Shi
The dopamine D2 and D3 receptors (D2R and D3R) are important targets for antipsychotics and for the treatment of drug abuse. SB269652, a bitopic ligand that simultaneously binds both the orthosteric binding site (OBS) and a secondary binding pocket (SBP) in both D2R and D3R, was found to be a negative allosteric modulator. Previous studies identified Glu2.65 in the SBP to be a key determinant of both the affinity of SB269652 and the magnitude of its cooperativity with orthosteric ligands, as the E2.65A mutation decreased both of these parameters...
January 16, 2018: PLoS Computational Biology
John Howl, Lewis Howl, Sarah Jones
Mastoparan (MP) peptides, distributed in insect venoms, induce a local inflammatory response post envenomation. Most endogenous MPs share common structural elements within a tetradecapeptide sequence that adopts an amphipathic helix whilst traversing biological membranes and when bound to an intracellular protein target. Rational modifications to increase cationic charge density and amphipathic helicity engineered mitoparan (MitP), a mitochondriotoxic bioportide and potent secretagogue. Following intracellular translocation, MitP is accreted by mitochondria thus indicating additional utility as an antimicrobial agent...
January 11, 2018: Peptides
Jing-Rong Fan, Hong-Xing Zhang, Yu-Guang Mu, Qing-Chuan Zheng
The transcription regulator teicoplanin-associate locus regulator (TcaR) plays a vital role in interfering with ssDNA replication and resisting ssDNA phage invasion. Although recent studies demonstrated that TcaR had strong interaction with ssDNA, the dynamics and interaction mechanism of dimeric TcaR bound to ssDNA have not been rationalized at the atomic level. In our study, MD simulations combined with MM-GB/SA calculations were employed to study recognition mechanism between TcaR and ssDNA. The results illuminate that electrostatic interaction is the main driving force for the binding process...
December 5, 2017: Journal of Molecular Graphics & Modelling
Sirimuvva Tadepalli, Jieun Yim, Sisi Cao, Zheyu Wang, Rajesh R Naik, Srikanth Singamaneni
Interfacing biomolecules with functional materials is a key strategy toward achieving externally-triggered biological function. The rational integration of functional proteins, such as enzymes, with plasmonic nanostructures that exhibit unique optical properties such as photothermal effect provides a means to externally control the enzyme activity. However, due to the labile nature of enzymes, the photothermal effect of plasmonic nanostructures is mostly utilized for the enhancement of the biocatalytic activity of thermophilic enzymes...
January 11, 2018: Small
Tetsuya Hori, Toshiaki Okuno, Kunio Hirata, Keitaro Yamashita, Yoshiaki Kawano, Masaki Yamamoto, Masakatsu Hato, Motonao Nakamura, Takao Shimizu, Takehiko Yokomizo, Masashi Miyano, Shigeyuki Yokoyama
Most G-protein-coupled receptors (GPCRs) are stabilized in common in the inactive state by the formation of the sodium ion-centered water cluster with the conserved Asp2.50 inside the seven-transmembrane domain. We determined the crystal structure of the leukotriene B4 (LTB4) receptor BLT1 bound with BIIL260, a chemical bearing a benzamidine moiety. Surprisingly, the amidine group occupies the sodium ion and water locations, interacts with D662.50, and mimics the entire sodium ion-centered water cluster. Thus, BLT1 is fixed in the inactive state, and the transmembrane helices cannot change their conformations to form the active state...
January 8, 2018: Nature Chemical Biology
Ari Hardianto, Muhammad Yusuf, Fei Liu, Shoba Ranganathan
BACKGROUND: (-)-Balanol is an ATP mimic that inhibits protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity. While PKA is a tumour promoter, PKC isozymes act as tumour promoters or suppressors, depending on the cancer type. In particular, PKCε is frequently implicated in cancer promotion, making it a potential target for anticancer drugs. To improve isozyme selectivity of balanol, exhaustive structural and activity relationship (SAR) studies have been performed in the last two decades, but with limited success...
December 28, 2017: BMC Bioinformatics
Chuanjiang He, Shu Zheng, Yan Luo, Ben Wang
Exosomes are common membrane-bound nanovesicles that contain diverse biomolecules, such as lipids, proteins, and nucleic acids. Exosomes are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Exosome secretion is a constitutive phenomenon that is involved in both physiological and pathological processes and determines both the exosomal surface molecules and the contents. Hence, we can exploit exosomes as biomarkers, vaccines and drug carriers and modify them rationally for therapeutic interventions...
2018: Theranostics
Gerwyn Morris, Michael Berk, André F Carvalho, Michael Maes, Adam J Walker, Basant K Puri
Ferroptosis is a unique form of programmed death, characterised by cytosolic accumulation of iron, lipid hydroperoxides and their metabolites, and effected by the fatal peroxidation of polyunsaturated fatty acids in the plasma membrane. It is a major driver of cell death in neurodegenerative neurological diseases. Moreover, cascades underpinning ferroptosis could be active drivers of neuropathology in major psychiatric disorders. Oxidative and nitrosative stress can adversely affect mechanisms and proteins governing cellular iron homeostasis, such as the iron regulatory protein/iron response element system, and can ultimately be a source of abnormally high levels of iron and a source of lethal levels of lipid membrane peroxidation...
December 28, 2017: Behavioural Brain Research
Marzena Mazur, Jacek Olczak, Sylwia Olejniczak, Robert Koralewski, Wojciech Czestkowski, Anna Jedrzejczak, Jakub Golab, Karolina Dzwonek, Barbara Dymek, Piotr L Sklepkiewicz, Agnieszka Zagozdzon, Tom Noonan, Keyvan Mahboubi, Bruce Conway, Ryan Sheeler, Paul Beckett, William M Hungerford, Alberto D Podjarny, Andre Mitschler, Alexandra Cousido-Siah, Firas Fadel, Adam Golebiowski
This article highlights our work toward the identification of a potent, selective, and in vivo efficacious acidic mammalian chitinase (AMCase) inhibitor. Rational design, guided by X-ray analysis of several inhibitors bound to human chitotriosidase (hCHIT1) led to the identification of compound 7f as a highly potent, AMCase inhibitor (IC50 values of 14 and 19 nM against human and mouse enzyme, respectively) and selective (>150x against mCHIT1) with very good PK properties. This compound dosed once daily at 30 mg/kg p...
December 28, 2017: Journal of Medicinal Chemistry
Jiyeon Han, Hyuck Jin Lee, Kyu Yeon Kim, Shin Jung C Lee, Jong-Min Suh, Jaeheung Cho, Junghyun Chae, Mi Hee Lim
Multiple pathogenic factors [e.g., amyloid-β (Aβ), metal ions, metal-bound Aβ (metal-Aβ), reactive oxygen species (ROS)] are found in the brain of patients with Alzheimer's disease (AD). In order to elucidate the roles of pathological elements in AD, chemical tools able to regulate their activities would be valuable. Due to the complicated link among multiple pathological factors, however, it has been challenging to invent such chemical tools. Herein, we report novel small molecules as chemical tools toward modulation of single or multiple target(s), designed via a rational structure-property-directed strategy...
December 28, 2017: ACS Chemical Neuroscience
Kan Sato, Rieka Ichinoi, Ryusuke Mizukami, Takuma Serikawa, Yusuke Sasaki, Jodie L Lutkenhaus, Hiroyuki Nishide, Kenichi Oyaizu
Charge transport processes in non-conjugated redox-active polymers with electrolytes were studied using a diffusion-cooperative model. For the first time, we quantitatively rationalized that the limited Brownian motion of the redox centers bound to the polymers resulted in the 103-4-fold decline of the bimolecular and heterogeneous charge transfer rate constants, which had been unexplained for half a century. As a next-generation design, a redox-active supramolecular system with high physical mobility was proposed to achieve the rate constant as high as in free solution system (>107 M-1s-1) and populated site density (> 1 mol/L)...
December 25, 2017: Journal of the American Chemical Society
Jonah Cheung, Arshad Mahmood, Ravi Kalathur, Lixuan Liu, Paul R Carlier
Malaria is a devastating disease in sub-Saharan Africa and is transmitted by the mosquito Anopheles gambiae. While indoor residual spraying of anticholinesterase insecticides has been useful in controlling the spread of malaria, widespread application of these compounds has led to the rise of an insecticide-resistant mosquito strain that harbors a G119S mutation in the nervous system target enzyme acetylcholinesterase. We demonstrate the atomic basis of insecticide resistance through structure determination of the G119S mutant acetylcholinesterase of An...
December 16, 2017: Structure
Ursula Kahler, Julian E Fuchs, Peter Goettig, Klaus R Liedl
A ten microsecond molecular dynamics simulation of a kallikrein-related peptidase 7 peptide complex revealed an unexpected change in binding mode. After more than two microseconds unrestrained sampling we observe a spontaneous transition of the binding pose including a 180 degree rotation around the P1 residue. Subsequently, the substrate peptide occupies the prime side region rather than the cognate non-prime side in a stable conformation. We characterize the unexpected binding mode in terms of contacts, solvent-accessible surface area, molecular interactions and energetic properties...
December 6, 2017: Journal of Biomolecular Structure & Dynamics
Andrea Astolfi, Giuseppe Manfroni, Violetta Cecchetti, Maria Letizia Barreca
We herein review all the currently available PDB ATP-site and non-ATP-site ligands bound to p38α MAPK. The co-crystallized inhibitors have been classified into different families according to their experimental binding mode and chemical structure, and the ligand-protein interactions discussed using the most representative compounds. This systematic structural analysis could provide take-home lessons for drug discovery programs aimed at the rational identification and optimization of new p38α MAPK inhibitors...
December 6, 2017: ChemMedChem
Kai Huang, Haichun Liu, Marco Kraft, Swati Shikha, Xiang Zheng, Hans Ågren, Christian Würth, Ute Resch-Genger, Yong Zhang
Lanthanide-doped upconversion nanoparticles (UCNPs) are of great interest for biomedical applications. Currently, the applicability of UCNP bionanotechnology is hampered by the generally low luminescence intensity of UCNPs and inefficient energy transfer from UCNPs to surface-bound chromophores used e.g. for photodynamic therapy or analyte sensing. In this work, we address the low-efficiency issue by developing versatile core-shell nanostructures, where high-concentration sensitizers and activators are confined in the core and shell region of representative hexagonal NaYF4:Yb,Er UCNPs...
December 6, 2017: Nanoscale
Sylvia Naliaka Marango, Christopher Khayeka-Wandabwa, Judith Alice Makwali, Bernard Ngoitsi Jumba, Joseph K Choge, Eric Onyango Adino, Christopher O Anjili
BACKGROUND: Conventional targeted leishmanicidal chemotherapy has persistently remained prohibitive for most economically deprived communities due to costs, associated time to accessing health services and duration for successful treatment programme. Alternatives are bound to be incorporated in rational management of leishmaniasis by choice or default due to accessibility and cultural beliefs. Therefore, there is need to rigorously investigate and appraise the activity of medicinal compounds that may have anti-leishmanicidal activity especially in the context of products that are already being utilized by the populations for other ailments but have limited information on their therapeutic value and possible cytoxicity...
December 6, 2017: BMC Research Notes
Lawrence Que, Johannes E M N Klein, Apparao Draksharapu, Alireza Shokri, Christopher J Cramer
The correlation between oxidation state and Lewis acidity is well established for hexaquairon complexes in the +II and +III oxidation state, where the higher oxidation state leads to a lower pKa for the bound H2O ligand. This article addresses the Lewis acidity of the oxoiron(IV) complex [FeIV(O)(TMC)(OH2)]2+ (1-OH2; TMC = 1,4,8,11-tetramethylcyclam) by determining the pKa of the H2O ligand. We establish that 1-OH2 has a pKa of 6.9±0.5, a value that falls in between those found for [FeIII(OH2)6]3+ and [FeII(OH2)6]2+...
December 2, 2017: Chemistry: a European Journal
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