The HDOCK server (http://hdock.phys.hust.edu.cn/) is a highly integrated suite of homology search, template-based modeling, structure prediction, macromolecular docking, biological information incorporation and job management for robust and fast protein-protein docking. With input information for receptor and ligand molecules (either amino acid sequences or Protein Data Bank structures), the server automatically predicts their interaction through a hybrid algorithm of template-based and template-free docking. The HDOCK server distinguishes itself from similar docking servers in its ability to support amino acid sequences as input and a hybrid docking strategy in which experimental information about the protein-protein binding site and small-angle X-ray scattering can be incorporated during the docking and post-docking processes. Moreover, HDOCK also supports protein-RNA/DNA docking with an intrinsic scoring function. The server delivers both template- and docking-based binding models of two molecules and allows for download and interactive visualization. The HDOCK server is user friendly and has processed >30,000 docking jobs since its official release in 2017. The server can normally complete a docking job within 30 min.

The HDOCK server for integrated protein-protein docking.

Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity.

Allosteric transition, defined as conformational changes induced by ligand binding, is one of the fundamental properties of proteins. Allostery has been observed and characterized in many proteins, and has been recently utilized to control protein function via regulation of protein activity. Here, we review the physical and evolutionary origin of protein allostery, as well as its importance to protein regulation, drug discovery, and biological processes in living systems. We describe recently developed approaches to identify allosteric pathways, connected sets of pairwise interactions that are responsible for propagation of conformational change from the ligand-binding site to a distal functional site. We then present experimental and computational protein engineering approaches for control of protein function by modulation of allosteric sites. As an example of application of these approaches, we describe a synergistic computational and experimental approach to rescue the cystic-fibrosis-associated protein cystic fibrosis transmembrane conductance regulator, which upon deletion of a single residue misfolds and causes disease. This example demonstrates the power of allosteric manipulation in proteins to both elucidate mechanisms of molecular function and to develop therapeutic strategies that rescue those functions. Allosteric control of proteins provides a tool to shine a light on the complex cascades of cellular processes and facilitate unprecedented interrogation of biological systems.

Controlling Allosteric Networks in Proteins.

This paper is a report of a second round of RNA-Puzzles, a collective and blind experiment in three-dimensional (3D) RNA structure prediction. Three puzzles, Puzzles 5, 6, and 10, represented sequences of three large RNA structures with limited or no homology with previously solved RNA molecules. A lariat-capping ribozyme, as well as riboswitches complexed to adenosylcobalamin and tRNA, were predicted by seven groups using RNAComposer, ModeRNA/SimRNA, Vfold, Rosetta, DMD, MC-Fold, 3dRNA, and AMBER refinement. Some groups derived models using data from state-of-the-art chemicalmapping methods (SHAPE, DMS, CMCT, and mutate-and-map). The comparisons between the predictions and the three subsequently released crystallographic structures, solved at diffraction resolutions of 2.5–3.2 A, were carried out automatically using various sets of quality indicators. The comparisons clearly demonstrate the state of present-day de novo prediction abilities as well as the limitations of these state-of-the-art methods. All of the best prediction models have similar topologies to the native structures, which suggests that computational methods for RNA structure prediction can already provide useful structural information for biological problems. However, the prediction accuracy for non-Watson–Crick interactions, key to proper folding of RNAs, is low and some predicted models had high Clash Scores. These two difficulties point to some of the continuing bottlenecks in RNA structure prediction. All submitted models are available for download at http://ahsoka.u-strasbg .fr/rnapuzzles/.

/pdf/rna-puzzles-round-ii-assessment-of-rna-structure-prediction-3mhdcvlak0.pdf

RNA-Puzzles Round II: assessment of RNA structure prediction programs applied to three large RNA structures

RNA-Puzzles is a collective experiment in blind 3D RNA structure prediction. We report here a third round of RNA-Puzzles. Five puzzles, 4, 8, 12, 13, 14, all structures of riboswitch aptamers and puzzle 7, a ribozyme structure, are included in this round of the experiment. The riboswitch structures include biological binding sites for small molecules (S-adenosyl methionine, cyclic diadenosine monophosphate, 5-amino 4-imidazole carboxamide riboside 5'-triphosphate, glutamine) and proteins (YbxF), and one set describes large conformational changes between ligand-free and ligand-bound states. The Varkud satellite ribozyme is the most recently solved structure of a known large ribozyme. All puzzles have established biological functions and require structural understanding to appreciate their molecular mechanisms. Through the use of fast-track experimental data, including multidimensional chemical mapping, and accurate prediction of RNA secondary structure, a large portion of the contacts in 3D have been predicted correctly leading to similar topologies for the top ranking predictions. Template-based and homology-derived predictions could predict structures to particularly high accuracies. However, achieving biological insights from de novo prediction of RNA 3D structures still depends on the size and complexity of the RNA. Blind computational predictions of RNA structures already appear to provide useful structural information in many cases. Similar to the previous RNA-Puzzles Round II experiment, the prediction of non-Watson-Crick interactions and the observed high atomic clash scores reveal a notable need for an algorithm of improvement. All prediction models and assessment results are available at http://ahsoka.u-strasbg.fr/rnapuzzles/.

/pdf/rna-puzzles-round-iii-3d-rna-structure-prediction-of-five-4uvt30773t.pdf

RNA-Puzzles Round III: 3D RNA structure prediction of five riboswitches and one ribozyme

Building tertiary structures of non-coding RNA is required to understand their functions and design new molecules. Current algorithms of RNA tertiary structure prediction give satisfactory accuracy only for small size and simple topology and many of them need manual manipulation. Here, we present an automated and fast program,3dRNA, for RNA tertiary structure prediction with reasonable accuracy for RNAs of larger size and complex topology.

/pdf/automated-and-fast-building-of-three-dimensional-rna-3w8fitbsab.pdf

Automated and fast building of three-dimensional RNA structures

Mapping the research hotspots and theme trends of simulation in nursing education: A bibliometric analysis from 2005 to 2019.

Background: Resilience has become a hot spot in the field of positive psychology to study life-change events. However, there were little information on resilience among the fathers and mothers of patients with cleft lip and/or palate respectively. The present study aimed to explore and compare the level and potential influential factors associated with resilience among fathers/mothers of patients with cleft lip and/or palate in China. Method: A cross-sectional study was carried out between April 2019 and July 2020 among fathers/mothers of patients with cleft lip and/or palate in two cleft lip and/or palate treatment centers in China. Sixty Nine fathers and 179 mothers of patients with cleft lip and/or palate were interviewed with a questionnaire on demographic variables and the Resilience Scale-14 (RS-14), Herth Hope Index (HHI), Multidimensional Scale of Perceived Social Support (MSPSS), Revised Life Orientation Test (LOT-R), Parenting Stress Index-Short Form (PSI-SF) and Coping Health Inventory for Parents (CHIP). T-test/univariate one-way ANOVA, Pearson's r, hierarchical linear regression analysis were conducted to explore the influential factors of resilience. Results: Fathers of patients with cleft lip and/or palate had a higher level of resilience (77.77 ± 14.18) than mothers (74.52 ± 14.33) though without significance. Resilience was positively associated with hope, perceived social support, optimism and coping and negatively correlated with parenting stress both in the fathers and the mothers. Hierarchical linear regression analysis showed that hope (β = 0.400, P < 0.01), coping (β = 0.281, P < 0.05), job status, medical payments (β = −0.240, P < 0.05) were found to be associated with resilience among the fathers of patients with CL/P, and all four variables in the model could explain 42.8% of the variance in resilience; Hope (β = 0.225, P < 0.05), perceived social support (β = 0.194, P < 0.05), the age of patients (β = 0.189, P < 0.05) were found to be associated with resilience among the mothers, and all three variables in the model could explain 27.6% of the variance in resilience. Conclusion: Our study showed that, in China, fathers of patients with cleft lip and/or palate had a higher level of resilience than mothers though without significance. Hope was the only communal variable strongly associated with resilience among both the fathers and the mothers; besides, coping, job status and medical payments were found to be associated with resilience among the fathers; while perceived social support and the age of patients were found to be associated with resilience among the mothers. The results suggest that enhance hope in parents of patients with cleft lip and/or palate might greatly help improve their resilience. Besides, fathers and mothers need specific intervention to prompt their resilience.

Yanjie Wang

Papers

Automated and fast building of three-dimensional RNA structures

Mapping the research hotspots and theme trends of simulation in nursing education: A bibliometric analysis from 2005 to 2019.

Resilience and Related Factors: A Comparison of Fathers and Mothers of Patients With Cleft Lip and/or Palate in China