Journal Articles
Modeling conformational redox-switch modulation of human succinic semialdehyde dehydrogenase
Succinic semialdehyde dehydrogenase (SSADH) converts succinic semialdehyde (SSA) to succinic acid in the mitochondrial matrix and is involved in the metabolism of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). The molecular structure of human SSADH revealed the intrinsic regulatory mechanism—redox-switch modulation—by which large conformational changes are brought about in the catalytic loop through disulfide bonding. The crystal structures revealed two SSADH conformations, and computational modeling of transformation between them can provide substantial insights into detailed dynamic redox modulation. On the basis of these two clear crystal structures, we modeled the conformational motion between these structures in silico. For that purpose, we proposed and used a geometry-based coarse-grained mathematical model of long-range protein motion and the related modeling algorithm. The algorithm is based on solving the special optimization problem, which is similar to the classical Monge–Kantorovich mass transportation problem. The modeled transformation was supported by another morphing method based on a completely different framework. The result of the modeling facilitates better interpretation and understanding of the SSADH biological role. Proteins 2015; 83:2217–2229. © 2015 Wiley Periodicals, Inc.
Protein structure refinement with adaptively restrained homologous replicas
A novel protein refinement protocol is presented which utilizes molecular dynamics (MD) simulations of an ensemble of adaptively restrained homologous replicas. This approach adds evolutionary information to the force field and reduces random conformational fluctuations by coupling of several replicas. It is shown that this protocol refines the majority of models from the CASP11 refinement category and that larger conformational changes of the starting structure are possible than with current state of the art methods. The performance of this protocol in the CASP11 experiment is discussed. We found that the quality of the refined model is correlated with the structural variance of the coupled replicas, which therefore provides a good estimator of model quality. Furthermore, some remarkable refinement results are discussed in detail. Proteins 2015. © 2015 Wiley Periodicals, Inc.
R248Q mutation—Beyond p53-DNA binding
R248 in the DNA binding domain (DBD) of p53 interacts directly with the minor groove of DNA. Earlier nuclear magnetic resonance (NMR) studies indicated that the R248Q mutation resulted in conformation changes in parts of DBD far from the mutation site. However, how information propagates from the mutation site to the rest of the DBD is still not well understood. We performed a series of all-atom molecular dynamics (MD) simulations to dissect sterics and charge effects of R248 on p53-DBD conformation: (i) wild-type p53 DBD; (ii) p53 DBD with an electrically neutral arginine side-chain; (iii) p53 DBD with R248A; (iv) p53 DBD with R248W; and (v) p53 DBD with R248Q. Our results agree well with experimental observations of global conformational changes induced by the R248Q mutation. Our simulations suggest that both charge- and sterics are important in the dynamics of the loop (L3) where the mutation resides. We show that helix 2 (H2) dynamics is altered as a result of a change in the hydrogen bonding partner of D281. In turn, neighboring L1 dynamics is altered: in mutants, L1 predominantly adopts the recessed conformation and is unable to interact with the major groove of DNA. We focused our attention the R248Q mutant that is commonly found in a wide range of cancer and observed changes at the zinc-binding pocket that might account for the dominant negative effects of R248Q. Furthermore, in our simulations, the S6/S7 turn was more frequently solvent exposed in R248Q, suggesting that there is a greater tendency of R248Q to partially unfold and possibly lead to an increased aggregation propensity. Finally, based on the observations made in our simulations, we propose strategies for the rescue of R248Q mutants. Proteins 2015; 83:2240–2250. © 2015 Wiley Periodicals, Inc.
Ensemble Methods Enable a New Definition for the Solution to Gas-Phase Transfer of Intrinsically Disordered Proteins
Chemiresistive Sensor Arrays from Conductive 2D Metal–Organic Frameworks
A New Tool for NMR Crystallography: Complete 13C/15N Assignment of Organic Molecules at Natural Isotopic Abundance Using DNP-Enhanced Solid-State NMR
Three-Coordinate Iron(IV) Bisimido Complexes with Aminocarbene Ligation: Synthesis, Structure, and Reactivity
Power struggle
Power struggle
Nature 526, 7575 (2015). doi:10.1038/526609a
The UK government’s decision to subsidize a nuclear power station while cutting support for renewables is short-sighted.
Massive UK baby study cancelled
Massive UK baby study cancelled
Nature 526, 7575 (2015). http://www.nature.com/doifinder/10.1038/526620a
Author: Helen Pearson
Loss prompts rethink about design of future cradle-to-grave studies.
Sensorimotor Model of Obstacle Avoidance in Echolocating Bats
by Dieter Vanderelst, Marc W. Holderied, Herbert Peremans
Bat echolocation is an ability consisting of many subtasks such as navigation, prey detection and object recognition. Understanding the echolocation capabilities of bats comes down to isolating the minimal set of acoustic cues needed to complete each task. For some tasks, the minimal cues have already been identified. However, while a number of possible cues have been suggested, little is known about the minimal cues supporting obstacle avoidance in echolocating bats. In this paper, we propose that the Interaural Intensity Difference (IID) and travel time of the first millisecond of the echo train are sufficient cues for obstacle avoidance. We describe a simple control algorithm based on the use of these cues in combination with alternating ear positions modeled after the constant frequency bat Rhinolophus rouxii. Using spatial simulations (2D and 3D), we show that simple phonotaxis can steer a bat clear from obstacles without performing a reconstruction of the 3D layout of the scene. As such, this paper presents the first computationally explicit explanation for obstacle avoidance validated in complex simulated environments. Based on additional simulations modelling the FM bat Phyllostomus discolor, we conjecture that the proposed cues can be exploited by constant frequency (CF) bats and frequency modulated (FM) bats alike. We hypothesize that using a low level yet robust cue for obstacle avoidance allows bats to comply with the hard real-time constraints of this basic behaviour.SnS44–, SbS43–, and AsS33– Metal Chalcogenide Surface Ligands: Couplings to Quantum Dots, Electron Transfers, and All-Inorganic Multilayered Quantum Dot Sensitized Solar Cells
A Simple and Facile Approach to Aliphatic N-Substituted Functional Eight-Membered Cyclic Carbonates and Their Organocatalytic Polymerization
Total Synthesis of Epoxyeujindole A
Tuning the Electromechanical Properties of Single DNA Molecular Junctions
CytoSpectre: a tool for spectral analysis of oriented structures on cellular and subcellular levels
Unravelling the Impact of Reaction Paths on Mechanical Degradation of Intercalation Cathodes for Lithium-Ion Batteries
Fungal pathogen uses sex pheromone receptor for chemotropic sensing of host plant signals
Fungal pathogen uses sex pheromone receptor for chemotropic sensing of host plant signals
Nature 527, 7579 (2015). doi:10.1038/nature15516
Authors: David Turrà, Mennat El Ghalid, Federico Rossi & Antonio Di Pietro
For more than a century, fungal pathogens and symbionts have been known to orient hyphal growth towards chemical stimuli from the host plant. However, the nature of the plant signals as well as the mechanisms underlying the chemotropic response have remained elusive. Here we show that directed growth of the soil-inhabiting plant pathogen Fusarium oxysporum towards the roots of the host tomato (Solanum lycopersicum) is triggered by the catalytic activity of secreted class III peroxidases, a family of haem-containing enzymes present in all land plants. The chemotropic response requires conserved elements of the fungal cell integrity mitogen-activated protein kinase (MAPK) cascade and the seven-pass transmembrane protein Ste2, a functional homologue of the Saccharomyces cerevisiae sex pheromone α receptor. We further show that directed hyphal growth of F. oxysporum towards nutrient sources such as sugars and amino acids is governed by a functionally distinct MAPK cascade. These results reveal a potentially conserved chemotropic mechanism in root-colonizing fungi, and suggest a new function for the fungal pheromone-sensing machinery in locating plant hosts in a complex environment such as the soil.
