Template-based modeling and ab-initio docking using CoDock in CAPRI

Integration of template-based modeling, global sampling and precise scoring is crucial for the development of molecular docking programs with improved accuracy. We combined template-based modeling and ab-initio docking protocol as hybrid docking strategy called CoDock for the docking and scoring experiments of the seventh CAPRI edition. For CAPRI rounds 38-45, we obtained acceptable or better models in the top 10 submissions for eight out of the 16 evaluated targets as predictors, nine out of the 16 targets as scorers. Especially, we submitted acceptable models for all of the evaluated protein-oligosaccharide targets. For the CASP13-CAPRI experiment (round 46), we obtained acceptable or better models in the top 5 submissions for 10 out of the 20 evaluated targets as predictors, 11 out of the 20 targets as scorers. The failed cases for our group were mainly the difficult targets and the protein-peptide systems in CAPRI and CASP13-CAPRI experiments. In summary, this CAPRI edition showed that our hybrid docking strategy can be efficiently adapted to the increasing variety of challenges in the field of molecular interactions.     

C1188D mutation abolishes specific recognition between MLL1-CXXC domain and CpG site by inducing conformational switch of flexible N-terminal

Mixed lineage leukemia protein (MLL1 protein) recognizes the CpG site via its CXXC domain and is frequently associated with leukemia. The specific recognition is abolished by C1188D mutation, which also prevents MLL-related leukemia. In this paper, multiple molecular dynamic (MD) simulations were performed to investigate the mechanism of recognition and influences of C1188D mutation. Started from fully dissociated DNA and MLL1-CXXC domain, remarkably, the center of mass (COM) of MLL1-CXXC domain quickly concentrates on the vicinity of the CpG site in all 53 short MD simulations. Extended simulations of the wild type showed that the native complex formed in 500 ns among 4 of 53 simulations. In contrast, the C1188D mutant COM distributed broadly around the DNA and the native complex was not observed in any of the extended simulations. Simulations on the apo MLL1-CXXC domain further suggest that the wild type protein remained predominantly in an open form that closely resembles its structure in the native complex whereas C1188D mutant formed predominantly compact structures in which the N- terminal bends to D1188. This conformational switch hinders the formation of encounter complex, thus abolishes the recognition. Our study also provides clues to the study mechanism of recognition, by the CXXC domain from proteins like DNA methyltransferase and ten-eleven translocation enzymes.     

Structural classification of αββ and ββα supersecondary structure units in proteins

We present a fully automatic structural classification of supersecondary structure units, consisting of two hydrogen-bonded β strands, preceded or followed by an α helix. The classification is performed on the spatial arrangement of the secondary structure elements, irrespective of the length and conformation of the intervening loops. The similarity of the arrangements is estimated by a structure alignment procedure that uses as similarity measure the root mean square deviation of superimposed backbone atoms. Applied to a set of 141 well-resolved nonhomologous protein structures, the classification yields 11 families of recurrent arrangements. In addition, fragments that are structurally intermediate between the families are found; they reveal the continuity of the classification. The analysis of the families shows that the α helix and β hairpin axes can adopt virtually all relative orientations, with, however, some preferable orientations; moreover, according to the orientation, preferences in the left/right handedness of the α–β connection are observed. These preferences can be explained by favorable side by side packing of the α helix and the β hairpin, local interactions in the region of the α–β connection or stabilizing environments in the parent protein. Furthermore, fold recognition procedures and structure prediction algorithms coupled to database-derived potentials suggest that the preferable nature of these arrangements does not imply their intrinsic stability. They usually accommodate a large number of sequences, of which only a subset is predicted to stabilize the motif. The motifs predicted as stable could correspond to nuclei formed at the very beginning of the folding process. Proteins 30:193–212, 1998. © 1998 Wiley-Liss, Inc.     

空间异质性对样地数据空间外推的影响

应用模型结合的方法模拟了3个空间异质性等级预案下反应变量(气候变化下景观水平的树种分布面积)的变化情况,并分析模拟结果在预案之间的差异性,探讨了环境空间异质性对样地观测到的树种对气候变化响应向更大空间尺度外推的影响.结果表明：空间异质性在一般情况下对样地数据向土地类型尺度外推没有影响,而对样地尺度外推到海拔带尺度的影响则有较复杂的情况.对于对气候变化不敏感的树种以及非地带性树种,空间异质性对样地数据向海拔带尺度外推没有影响;对于大多数对气候变化敏感的地带性树种而言,空间异质性对样地数据向海拔带尺度外推则有影响.     

The combined effects of energy and disturbance on species richness in protist microcosms

The supply of energy, and the frequency of disturbance can both affect species diversity, often, although not always, producing unimodal diversity patterns along an energy or disturbance gradient. However, it has been suggested that diversity is a combined function of both factors, and the dynamic equilibrium model proposed by Huston (1979) is one formalization of this suggestion. This idea has received little direct testing. Here we carry out such a test using protist microcosms, in a factorial manipulation of six levels of energy (quantity of organic resource) and five levels of disturbance (frequency of temperature shock). Species richness responded to both energy supply and disturbance frequency, although not always unimodally. Patterns of response changed over time, and there was some evidence of an interaction between energy and disturbance at two of six time intervals. However, the specific form of this interaction differs from that predicted by the dynamic equilibrium model, and overall, the results provide little support for the model.     

Fast and accurate modeling of protein-protein interactions by combining template-interface-based docking with flexible refinement

The similarity between folding and binding led us to posit the concept that the number of protein-protein interface motifs in nature is limited, and interacting protein pairs can use similar interface architectures repeatedly, even if their global folds completely vary. Thus, known protein-protein interface architectures can be used to model the complexes between two target proteins on the proteome scale, even if their global structures differ. This powerful concept is combined with a flexible refinement and global energy assessment tool. The accuracy of the method is highly dependent on the structural diversity of the interface architectures in the template dataset. Here, we validate this knowledge-based combinatorial method on the Docking Benchmark and show that it efficiently finds high-quality models for benchmark complexes and their binding regions even in the absence of template interfaces having sequence similarity to the targets. Compared to "classical" docking, it is computationally faster; as the number of target proteins increases, the difference becomes more dramatic. Further, it is able to distinguish binders from nonbinders. These features allow performing large-scale network modeling. The results on an independent target set (proteins in the p53 molecular interaction map) show that current method can be used to predict whether a given protein pair interacts. Overall, while constrained by the diversity of the template set, this approach efficiently produces high-quality models of protein-protein complexes. We expect that with the growing number of known interface architectures, this type of knowledge-based methods will be increasingly used by the broad proteomics community.     

NO serves as a signaling intermediate downstream of H2O2 to modulate dynamic microtubule cytoskeleton during responses to VD-toxins in Arabidopsis

Although hydrogen peroxide (H₂O₂) and nitric oxide (NO) can act as an upstream signaling molecule to modulate the dynamic microtubule cytoskeleton during the defense responses to Verticillium dahliae (VD) toxins in Arabidopsis, it is not known the relationship between these two signaling molecules. Here, we show that VD-toxin-induced NO accumulation was dependent on prior H₂O₂ production, NO is downstream of H₂O₂ in the signaling process, and that H₂O₂ acted synergistically with NO to modulate the dynamic microtubule cytoskeleton responses to VD-toxins in Arabidopsis.     

Viewing and annotating sequence data with Artemis

Artemis is a widely used software tool for annotating and viewing sequence data. No database is required to use Artemis. Instead, individual sequence data files can be analysed with little or no formatting, making it particularly suited to the study of small genomes and chromosomes, and straightforward for a novice user to get started. Since its release in 1999, Artemis has been used to annotate a diverse collection of prokaryotic and eukaryotic genomes, ranging from Streptomyces coelicolor to, more recently, a large proportion of the Plasmodium falciparum genome. Artemis allows annotated genomes to be easily browsed and makes it simple to add useful biological information to raw sequence data. This paper gives an overview of some of the features of Artemis and includes how it facilitates manual gene prediction and can provide an overview of entire chromosomes or small compact genomes--useful for uncovering unusual features such as pathogenicity islands.     

升流厌氧污泥层反应器动力学模型

用碘离子作示踪剂,采用矩形脉冲示踪法测定升流厌氧污泥层(UASB)反应器的流动分布。建立了申级返混加沟流模型。模型简单,能够反映反应器流动分布,具有较强的拟合能力和良好的适用性。运用流动模型和Monod方程,建立了UASB反应器稳态模型,并对模型参数进行了估计。通过灵敏度分析,进水基质浓度S。,废水流量Q,最大比基质降解速率,μmax 对出水基质浓度有较大影响。在稳态模型的基础上又建立了UASB反应器动态模态,利用此模型,对出水基质浓度序列Se,和产气量序列Qg进行计算预测,平均偏差分别5．40％和7．46％,标准偏差分别为7．02％和9．66％。     

Long‐term non‐equilibrium dynamics of insular floras: a 17‐year record

Aim To document long‐term rates of immigration, extinction and turnover in insular floras and evaluate the relative impacts of recent hurricane activity and climate change. Location Three archipelagos of small islands, in the Exuma Cays, Andros and Abacos, Bahamas. Methods I surveyed the floras of 194 vegetated islands in three archipelagos over several multi‐year periods, spanning up to 17 years. Changes in abundance (foliar cover) of persistent populations were measured on a subset of 14 islands in the Exuma Cays over a 9‐year period. Results Rates of plant turnover were generally low compared with other organisms, but varied among archipelagos and time periods. Turnover rates were usually higher in the second decade of this study, and extinction rates were often dramatically higher than immigration rates in the second decade, resulting in overall decreases in species richness. Turnover did not differ significantly among island types based on generalized location and surrounding water depths, and extinctions were not more likely to occur on more exposed islands. The abundance (foliar cover) of populations that did not go extinct decreased steadily over the second decade of this study, indicating, along with higher extinction rates, a generalized decline in these insular floras. Main conclusions Although some islands may have been at or near a state of dynamic equilibrium in the first decade of this study, average species richness declined in all three archipelagos during the second decade, when extinctions greatly outnumbered immigrations. Four major hurricanes affected the study archipelagos in the second decade of this study, although the available evidence suggests that the hurricanes were not directly responsible for the declines. Indirect effects of hurricanes such as increased herbivory and possible decreased nutrient availability, along with a long‐term (25 years) increase in temperature and decline in rainfall are likely contributing factors.