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.     

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.     

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.     

气候变化下中国八种梧桐属树种潜在适生区模拟

中国梧桐属（Firmiana）在世界梧桐属中占比较大,且除梧桐外其余种均为中国特有且分布范围狭窄的植物种,灭绝风险大,研究气候变化对中国梧桐属树种的影响对于维护生物多样性具有重要的意义。结合多时期第六次国际气候耦合模式比较计划（CMIP6）气候变量数据和中国八种梧桐属树种的分布数据,基于R语言kuenm程序包优化的最大熵（Maxent）模型模拟分析中国八种梧桐属树种在多尺度下的潜在适生区,得出梧桐属最适宜的模拟尺度、潜在适生区的面积变化和迁移方向、梧桐属多样性保护关键区域及保护空缺。结果表明：（1）梧桐属最适宜的模拟尺度为亚洲;（2） Maxent模型的接收者操作特征曲线下面积（AUC）值均大于0.9,表明模型对梧桐属潜在适生区预测结果具有较高准确度;（3）气候变化影响下除云南梧桐（Firmiana major）外其它树种的潜在适生区都将在未来有所扩大;（4）中国八种梧桐属树种潜在适生区迁移方向主要为东西向,南北向大跨度迁移较少,纬度变化不大;（5）丹霞梧桐（Firmiana danxiaensis）的稳定潜在适生区最小;（6）中国梧桐属多样性保护关键区域主要分布于广西壮族自治区及云南、广东、海南等省区;（7）中国梧桐属多样性保护空缺区域主要分布于广西壮族自治区中部及海南省北部;（8）梧桐属多样性保护关键区域正在为人造地表所侵蚀。研究分析气候变化对中国八种梧桐属树种的影响及其潜在适生区变化、中国梧桐属多样性保护状态,可为中国梧桐属建立多样性保护廊道提供相关建议,为制定多样性保护规划及相应措施提供参考。     

A unifying theory for methods of systematic analysis

A unifying theory for systematic analysis states that a number of methods should be used jointly to cope with various kinds of data; also that groups should be as consistent as possible, be made with least information loss, and where needed, be polythetic. A test of relationship, homogeneity, can use various kinds of data. It can take account of the internal variation of aggregate items such as genera. It can give due emphasis to smaller clusters that have likely important contexts of external items. It helps in analysing trends, cores and hazes in dendrograms. A proposed detector for formal groups can be based on measures of isolation, identifiability and inclusiveness. Non-mathematical, inter-item reaction tests such as hybridization and serology can also be used in grouping. All relationship data are used polythetically to reveal natural groups. This leads to a unified informational concept for taxa. This is more useful than the biological species concept that is restricted to inter-breeding data. All the methods appear to be analogues of the powerful human grouping instinct. The resulting compatibility is important as precise methods are needed mainly when the data are too complex for the mind to use reliably. Cladograms can be made by self-graded deweighting of homogeneity and agglomerative clustering. Unlike classical cladistics this can reveal any polythetic group. Finding the derived states for making cladograms is often much too hypothetical for a fully cladistic approach to be properly precise. Instead, where the evidence is weak, a milder strength of graded deweighting is used for the cladistic properties, which help to show relationships along with the others. Axiomatic failures of other classes of grouping methods are discussed. Unavoidable remnants of instinctive processing lower the precision of all the methods. The Uniter computer program, based on the theory, is tested with finely graded values of artificially ‘evolved’ items and with coarsely coded cladistic data. The results show that with natural data, the program should act as a fairly sensitive probe of past evolutionary branching. Another test shows how specimens from species complexes can be grouped and how distinctions between groups are analysed.     

Numerical and chemical classification ofStreptosporangium and some related actinomycetes

One hundred and seventeen streptosporangia from soil were compared with marker strains of the familyStreptosporangiaceae for many phenotypic properties. The data were examined using the Jaccard, pattern and simple matching coefficients with clustering achieved using average, complete and single linkage algorithms. Particular confidence was placed in the product of the pattern, average linkage analysis given the sharp definition of aggregate groups and clusters and a combination of low test error and high cophenetic correlation values. The test strains were assigned to five aggregate groups that were equated with the generaStreptosporangium (group A),Microbispora (group B),Planobispora andPlanomonospora (Group C),Kutzneria (neéStreptosporangium viridogriseum (group D), andMicrotetraspora (group E). The streptosporangia, both isolates and marker strains, were assigned to 5 major, 7 minor and 18 single membered clusters. Representative streptosporangia examined for chemical markers were characterised by the presence ofmeso-diaminopimelic acid in whole-organism hydrolysates, complex mixtures of straight- and branched chain fatty acids, di- and tetrahydrogenated menaquinones as predominant isoprenologues, and complex polar lipid patterns containing diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides and uncharacterised components. The chemical and numerical data support the taxonomic integrity of the validly described species ofStreptosporangium and suggest that the genus is markedly underspeciated.     

Microsecond simulations of mdm2 and its complex with p53 yield insight into force field accuracy and conformational dynamics

The p53‐MDM2 complex is both a major target for cancer drug development and a valuable model system for computational predictions of protein‐ligand binding. To investigate the accuracy of molecular simulations of MDM2 and its complex with p53, we performed a number of long (200 ns to 1 µs) explicit‐solvent simulations using a range of force fields. We systematically compared nine popular force fields (AMBER ff03, ff12sb, ff14sb, ff99sb, ff99sb‐ildn, ff99sb‐ildn‐nmr, ff99sb‐ildn‐phi, CHARMM22*, and CHARMM36) against experimental chemical shift data, and found similarly accurate results, with microsecond simulations achieving better agreement compared to 200‐ns trajectories. Although the experimentally determined apo structure has a closed binding cleft, simulations in all force fields suggest the apo state of MDM2 is highly flexible, and able to sample holo‐like conformations, consistent with a conformational selection model. Initial structuring of the MDM2 lid region, known to competitively bind the binding cleft, is also observed in long simulations. Taken together, these results show molecular simulations can accurately sample conformations relevant for ligand binding. We expect this study to inform future computational work on folding and binding of MDM2 ligands. Proteins 2015; 83:1665–1676. © 2015 Wiley Periodicals, Inc.     

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

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 chemical-mapping 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 Å, 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/.     

First partial three-dimensional model of human monoamine oxidase A

A survey of the major known structural aspects of monoamine oxidase (MAO) is given and a first partial model of human MAO A is presented. This 3D model has been established using secondary structure predictions and fold recognition methods. It shows two α/β domains (the FAD-binding N-terminal and central domains) and an α+β domain. The C-terminal region is predicted to be responsible for anchoring the protein into the mitochondrial membrane and was not modeled. The covalent binding of the flavin cofactor to a cysteine residue is well predicted. The model is validated with experimental data from the literature and should be useful in designing new experimental studies (site-directed mutagenesis, chemical modification, specific antibodies). This first step towards the 3D structure of monoamine oxidase should contribute to a better understanding of the mechanisms of action and inhibition of this drug target in the treatment of clinical depression. Proteins 32:97–110, 1998. © 1998 Wiley-Liss, Inc.