We report the results of residue‐residue contact prediction of a new pipeline built purely on the learning of coevolutionary features in the CASP13 experiment. For a query sequence, the pipeline ...starts with the collection of multiple sequence alignments (MSAs) from multiple genome and metagenome sequence databases using two complementary Hidden Markov Model (HMM)‐based searching tools. Three profile matrices, built on covariance, precision, and pseudolikelihood maximization respectively, are then created from the MSAs, which are used as the input features of a deep residual convolutional neural network architecture for contact‐map training and prediction. Two ensembling strategies have been proposed to integrate the matrix features through end‐to‐end training and stacking, resulting in two complementary programs called TripletRes and ResTriplet, respectively. For the 31 free‐modeling domains that do not have homologous templates in the PDB, TripletRes and ResTriplet generated comparable results with an average accuracy of 0.640 and 0.646, respectively, for the top L/5 long‐range predictions, where 71% and 74% of the cases have an accuracy above 0.5. Detailed data analyses showed that the strength of the pipeline is due to the sensitive MSA construction and the advanced strategies for coevolutionary feature ensembling. Domain splitting was also found to help enhance the contact prediction performance. Nevertheless, contact models for tail regions, which often involve a high number of alignment gaps, and for targets with few homologous sequences are still suboptimal. Development of new approaches where the model is specifically trained on these regions and targets might help address these problems.
Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for ...brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.
Charge redistribution on surface of Ru nanoparticle can significantly affect electrocatalytic HER activity. Herein, a double atomic‐tuned RuBi SAA/Bi@OG nanostructure that features RuBi single‐atom ...alloy nanoparticle supported by Bi−O single‐site‐doped graphene was successfully developed by one‐step pyrolysis method. The alloyed Bi single atom and adjacent Bi−O single site in RuBi SAA/Bi@OG can synergistically manipulate electron transfer on Ru surface leading to optimum charge redistribution. Thus, the resulting RuBi SAA/Bi@OG exhibits superior alkaline HER activity. Its mass activity is up to 65000 mA mg−1 at an overpotential of 150 mV, which is 72.2 times as much as that of commercial Pt/C. DFT calculations reveal that the RuBi SAA/Bi@OG possesses the optimum charge redistribution, which is most beneficial to strengthen adsorption of water and weaken hydrogen‐adsorption free energy in HER process. This double atomic‐tuned strategy on surface charge redistribution of Ru nanoparticle opens a new way to develop highly efficient electrocatalysts.
A double atomic‐tuned RuBi SAA/Bi@OG nanostructure was prepared by one‐step pyrolysis method. The electron density on surface of Ru nanoparticle can be synergistically modulated by alloyed Bi single atom and adjacent Bi−O single site leading to optimum charge redistribution. Thus, the resulting RuBi SAA/Bi@OG exhibits superior alkaline HER activity.
Designing and fabrication of highly active single-atom catalysts (SACs) with maximized atomic efficiency is highly desirable but still remains a great challenge. Herein, highly active and stable ...cobalt single-atoms with a Co–N 4 moiety were uniformly anchored on a porous porphyrinic triazine-based framework (CoSAs/PTF) by a simple ionothermal method. Due to the abundant single-atom Co–N 4 species, the hierarchical porous structure and the good conductivity, the resultant catalyst is highly active for the electrocatalytic oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER). For the ORR, a more positive half-wave potential of 0.808 V ( vs. RHE) was achieved, compared with commercial benchmark Pt/C (0.806 V). Furthermore, a small onset potential of 21 mV and a low Tafel slope of 50 mV per decade were obtained for the HER. The porphyrin-like structure was found to stabilize the CoSAs effectively, thus leading to long-term durability and a remarkable methanol-tolerant behavior. This bifunctional single-atom catalyst might be a promising candidate to replace Pt-based electrocatalysts in electrolysers and fuel cells.
Abstract
Motivation
Contact-map of a protein sequence dictates the global topology of structural fold. Accurate prediction of the contact-map is thus essential to protein 3D structure prediction, ...which is particularly useful for the protein sequences that do not have close homology templates in the Protein Data Bank.
Results
We developed a new method, ResPRE, to predict residue-level protein contacts using inverse covariance matrix (or precision matrix) of multiple sequence alignments (MSAs) through deep residual convolutional neural network training. The approach was tested on a set of 158 non-homologous proteins collected from the CASP experiments and achieved an average accuracy of 50.6% in the top-L long-range contact prediction with L being the sequence length, which is 11.7% higher than the best of other state-of-the-art approaches ranging from coevolution coupling analysis to deep neural network training. Detailed data analyses show that the major advantage of ResPRE lies at the utilization of precision matrix that helps rule out transitional noises of contact-maps compared with the previously used covariance matrix. Meanwhile, the residual network with parallel shortcut layer connections increases the learning ability of deep neural network training. It was also found that appropriate collection of MSAs can further improve the accuracy of final contact-map predictions. The standalone package and online server of ResPRE are made freely available, which should bring important impact on protein structure and function modeling studies in particular for the distant- and non-homology protein targets.
Availability and implementation
https://zhanglab.ccmb.med.umich.edu/ResPRE and https://github.com/leeyang/ResPRE.
Supplementary information
Supplementary data are available at Bioinformatics online.
Developing high‐energy‐density electrodes for lithium ion batteries (LIBs) is of primary importance to meet the challenges in electronics and automobile industries in the near future. Conversion ...reaction‐based transition metal oxides are attractive candidates for LIB anodes because of their high theoretical capacities. This review summarizes recent advances on the development of nanostructured transition metal oxides for use in lithium ion battery anodes based on conversion reactions. The oxide materials covered in this review include oxides of iron, manganese, cobalt, copper, nickel, molybdenum, zinc, ruthenium, chromium, and tungsten, and mixed metal oxides. Various kinds of nanostructured materials including nanowires, nanosheets, hollow structures, porous structures, and oxide/carbon nanocomposites are discussed in terms of their LIB anode applications.
Conversion reaction‐based oxides are considered promising anode materials to replace graphite due to their high theoretical capacity. This review summarizes recent advances in the development of nanostructured transition metal oxides for use in lithium ion battery anodes based on conversion reactions. Moreover, some important aspects and future directions for designing high‐performance anodes are discussed.
Tuning the side chains of conjugated polymers is a simple, yet effective strategy for modulating their structural and electrical properties, but their impact on n‐type conjugated polymers has not ...been studied extensively, particularly in the area of all‐polymer solar cells (all‐PSCs). Herein, the effects of side chain engineering of P(NDI2OD‐T2) polymer (also known as Polyera Activink N2200) are investigated, which is the most widely used n‐type polymer in all‐PSCs and organic field‐effect transistors (OFETs), on their structural and electronic properties. A series of naphthalenediimide‐bithiophene‐based copolymers (P(NDIR‐T2)) is synthesized, with different side chains (R) of 2‐hexyldecyl (2‐HD), 2‐octyldodecyl (2‐OD), and 2‐decyltetradecyl (2‐DT). The P(NDI2HD‐T2) exhibits more noticeable crystalline behaviors than P(NDI2OD‐T2) and P(NDI2DT‐T2), thereby facilitating superior 3D charge transport. For example, the P(NDI2HD‐T2) shows the highest OFET electron mobility (1.90 cm2 V−1 s−1). Also, a series of all‐PSCs is produced using different electron donors of PTB7‐Th, PTB7, and PPDT2FBT. The P(NDI2HD‐T2) based all‐PSCs produce much higher power conversion efficiency (PCE) irrespective of the electron donors. In particular, the PTB7‐Th:P(NDI2HD‐T2) forms highly ordered, strong face‐on interchain stackings, and has better intermixed bulk‐heterojunction morphology, producing the highest PCE of 6.11% that has been obtained by P(NDIR‐T2) based all‐PSCs to date.
The effect of side chain modification of naphthalenediimide–bithiophene (NDI‐T2)‐based n‐type polymers on their structural and electronic properties has been investigated. The P(NDI2HD‐T2)‐based all‐polymer solar cells produce much better performance than other NDI‐T2‐based devices (i.e., P(NDI2OD‐T2) (Polyera Activink N2200)) irrespective of the electron donor due to superb electron transport ability of P(NDI2HD‐T2).
This article reports and analyzes the results of protein contact and distance prediction by our methods in the 14th Critical Assessment of techniques for protein Structure Prediction (CASP14). A new ...deep learning‐based contact/distance predictor was employed based on the ensemble of two complementary coevolution features coupling with deep residual networks. We also improved our multiple sequence alignment (MSA) generation protocol with wholesale meta‐genome sequence databases. On 22 CASP14 free modeling (FM) targets, the proposed model achieved a top‐L/5 long‐range precision of 63.8% and a mean distance bin error of 1.494. Based on the predicted distance potentials, 11 out of 22 FM targets and all of the 14 FM/template‐based modeling (TBM) targets have correctly predicted folds (TM‐score >0.5), suggesting that our approach can provide reliable distance potentials for ab initio protein folding.
The Five-hundred-meter Aperture Spherical radio Telescope (FAST) has passed national acceptance and finished one pilot cycle of 'Shared-Risk' observations. It will start formal operation soon. In ...this context, this paper describes testing results of key fundamental parameters for FAST, aiming to provide basic support for observation and data reduction of FAST for scientific researchers. The 19-beam receiver covering 1.05-1.45 GHz was utilized for most of these observations. The fluctuation in electronic gain of the system is better than 1% over 3.5 hours, enabling enough stability for observations. Pointing accuracy, aperture efficiency and system temperature are three key parameters for FAST. The measured standard deviation of pointing accuracy is 7.9″, which satisfies the initial design of FAST. When zenith angle is less than 26.4°, the aperture efficiency and system temperature around 1.4 GHz are ∼0.63 and less than 24 K for central beam, respectively. The sensitivity and stability of the 19-beam backend are confirmed to satisfy expectation by spectral Hi observations toward NGC 672 and polarization observations toward 3C 286. The performance allows FAST to take sensitive observations for various scientific goals, from studies of pulsars to galaxy evolution.
Protein–ATP interactions are ubiquitous in a wide variety of biological processes. Correctly locating ATP binding sites from protein information is an important but challenging task for protein ...function annotation and drug discovery. However, there is no method that can optimally identify ATP binding sites for different proteins. In this study, we report a new composite predictor, ATPbind, for ATP binding sites by integrating the outputs of two template-based predictors (i.e., S-SITE and TM-SITE) and three discriminative sequence-driven features of proteins: position specific scoring matrix, predicted secondary structure, and predicted solvent accessibility. In ATPbind, we assembled multiple support vector machines (SVMs) based on a random undersampling technique to cope with the serious imbalance phenomenon between the numbers of ATP binding sites and of non-ATP binding sites. We also constructed a new gold-standard benchmark data set consisting of 429 ATP binding proteins from the PDB database to evaluate and compare the proposed ATPbind with other existing predictors. Starting from a query sequence and predicted I-TASSER models, ATPbind can achieve an average accuracy of 72%, covering 62% of all ATP binding sites while achieving a Matthews correlation coefficient value that is significantly higher than that of other state-of-the-art predictors.
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