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21.
A Monte Carlo algorithm that searches for the optimal docking configuration of hen egg white lysozyme to an antibody is developed. Both the lysozyme and the antibody are kept rigid. Unlike the work of other authors, our algorithm does not attempt to explicitly maximize surface contact, but minimizes the energy computed using coarse-grained pair potentials. The final refinement of our best solutions using all-atom OPLS potentials (Jorgensen and Tirado-Rives8) consistently yields the native conformation as the preferred solution for three different antibodies. We find that the use of an exponential distance-dependent dielectric function is an improvement over the more commonly used linear form. © 1993 Wiley-Liss, Inc. 相似文献
22.
青藏高原物种丰富且属于气候变化敏感区,研究气候变化对青藏高原物种的潜在分布影响,对于该区域物种多样性保护具有重要意义。该研究以一级濒危藏药植物全缘叶绿绒蒿为研究对象,利用加权平均算法(weighted average algorithm, WAA)构建随机森林(RF)、灵活判别分析(FDA)及人工神经网络(ANN)的集成模型,同时对比分析了WAA模型和不同生态位模型的预测精度。最后利用WAA模型预测了全缘叶绿绒蒿在当前(1970~2000年平均)和未来(2041~2060年平均)气候情景下的潜在分布,其中未来气候考虑了2种“共享社会经济路径”(SSP2-45和SSP5-85)。结果显示:(1) WAA模型的预测表明,基于RF、FDA和ANN的集成模型的AUC值为0.926,在AUC值最高RF模型的基础上提高了3%,在FDA和ANN模型的AUC值的基础上均提高了5%。(2) WAA模型确定,全缘叶绿绒蒿的潜在分布对年降水量和最暖季降水量最为敏感,其次是最热月份最高气温,同时对最湿月份降水量以及等温性表现出较低的敏感性。(3)当前全缘叶绿绒蒿潜在分布区主要分布在甘肃西南部、青海东部至南部、四川西部和西北部、云南西北部和东北部、西藏东部。(4)未来气候变化下青藏高原全缘叶绿绒蒿潜在分布预测表明,在2050年SSP2-45情景下,全缘叶绿绒蒿的潜在分布区大小与当前潜在分布区大小基本相同,但整体向西北方向高海拔高纬度地区迁移;在SSP5-85情景下,全缘叶绿绒蒿的潜在分布区明显收缩,且向西北高纬度高海拔地区延伸的趋势更加明显。 相似文献
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《Animal : an international journal of animal bioscience》2023,17(4):100727
The aim of this study is built in two phases: to quantify the ability of novel milk metabolites to measure between-animal variability in response and recovery profiles to a short-term nutritional challenge, then to derive a resilience index from the relationship between these individual variations. At two different stages of lactation, sixteen lactating dairy goats were exposed to a 2-d underfeeding challenge. The first challenge was in late lactation, and the second was carried out on the same goats early in the following lactation. During the entire experiment period, samples were taken at each milking for milk metabolite measures. For each metabolite, the response profile of each goat was characterised using a piecewise model for describing the dynamic pattern of response and recovery profiles after the challenge relative to the start of the nutritional challenge. Cluster Analysis identified three types of response/recovery profiles per metabolite. Using cluster membership, multiple correspondence analyses (MCAs) were performed to further characterise response profile types across animals and metabolites. This MCA analysis identified three groups of animals. Further, discriminant path analysis was able to separate these groups of multivariate response/recovery profile type based on threshold levels of three milk metabolites: β-hydroxybutyrate, free glucose and uric acid. Further analyses were done to explore the possibility of developing an index of resilience from milk metabolite measures. Different types of performance response to short-term nutritional challenge can be distinguished using multivariate analyses of a panel of milk metabolites. 相似文献
25.
Pearlman DA 《Journal of biomolecular NMR》1996,8(1):49-66
Summary A new NMR refinement method, FINGAR (FIt NMR using a Genetic AlgoRithm), has been developed, which allows one to determine a weighted set of structures that best fits measured NMR-derived data. This method shows appreciable advantages over commonly used refinement methods. FINGAR generates an ensemble of conformations whose average reproduces the experimental NMR-derived restraints. In addition, a statistical importance weight is assigned to each of the conformations in the ensemble. As a result, one is not limited to simply presenting an envelope of sampled conformers. Instead, one can subsequently focus on a select few conformers of high weight. This is critical, because many structural analyses depend on using discrete conformations, not simply averages or ensembles. The genetic algorithm used by FINGAR allows one to simultaneously and reliably fit against many restraints, and to generate solutions which include as many conformations with non-zero weights as are necessary to generate the best fit. An added benefit of FINGAR is that because the time-consuming step in this method needs only to be performed once, in the beginning of the first run, numerous FINGAR simulations can be performed rapidly. 相似文献
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G. A. Lazar J. R. Desjarlais T. M. Handel 《Protein science : a publication of the Protein Society》1997,6(6):1167-1178
We have previously reported the development and evaluation of a computational program to assist in the design of hydrophobic cores of proteins. In an effort to investigate the role of core packing in protein structure, we have used this program, referred to as Repacking of Cores (ROC), to design several variants of the protein ubiquitin. Nine ubiquitin variants containing from three to eight hydrophobic core mutations were constructed, purified, and characterized in terms of their stability and their ability to adopt a uniquely folded native-like conformation. In general, designed ubiquitin variants are more stable than control variants in which the hydrophobic core was chosen randomly. However, in contrast to previous results with 434 cro, all designs are destabilized relative to the wild-type (WT) protein. This raises the possibility that beta-sheet structures have more stringent packing requirements than alpha-helical proteins. A more striking observation is that all variants, including random controls, adopt fairly well-defined conformations, regardless of their stability. This result supports conclusions from the cro studies that non-core residues contribute significantly to the conformational uniqueness of these proteins while core packing largely affects protein stability and has less impact on the nature or uniqueness of the fold. Concurrent with the above work, we used stability data on the nine ubiquitin variants to evaluate and improve the predictive ability of our core packing algorithm. Additional versions of the program were generated that differ in potential function parameters and sampling of side chain conformers. Reasonable correlations between experimental and predicted stabilities suggest the program will be useful in future studies to design variants with stabilities closer to that of the native protein. Taken together, the present study provides further clarification of the role of specific packing interactions in protein structure and stability, and demonstrates the benefit of using systematic computational methods to predict core packing arrangements for the design of proteins. 相似文献
28.
Friedrichs MS 《Journal of biomolecular NMR》1995,5(2):147-153
Summary A novel algorithm for removing baseline distortions in NMR spectra is presented. The algorithm approximates the baseline as the median of the noise extrema. Consequently, the method does not require that NMR peaks be discriminated from noise peaks. In addition, no assumptions regarding the source or functional form of the distortion are made. The algorithm is shown to remove the baseline artifacts present in a particularly distorted NOESY spectrum and to reveal peaks which had been obscured by the artifacts. The parameters and spectral characteristics (signal-to-noise ratio, NMR peak density, peak linewidths) governing the resolution of the calculated baselines are also explored. 相似文献
29.
Limited proteolysis of native proteins: the interaction between avidin and proteinase K. 总被引:1,自引:1,他引:0 下载免费PDF全文
D. Ellison J. Hinton S. J. Hubbard R. J. Beynon 《Protein science : a publication of the Protein Society》1995,4(7):1337-1345
Avidin is a tetramer of 16-kDa subunits that have a high affinity for biotin. Proteolysis of native apoavidin by proteinase K results in a limited attack at the loop between beta-strands 3 and 4, involving amino acids 38-43. Specifically, sites of proteolysis are at Thr 40-Ser 41 and Asn 42-Glu 43. The limited proteolysis results in an avidin product that remains otherwise intact and which has enhanced binding for 4'-hydroxyazobenzene-2-benzoic acid (HABA), a chromogenic reporter that can occupy the biotin-binding site. Saturation of the biotin-binding site with the natural ligand protects avidin from proteolysis, but saturation with HABA enhances the rate of proteolysis of the same site. Analysis of the three-dimensional structures of apoavidin and holoavidin reveals that the 3-4 loop is accessible to solvent and scores highly in an algorithm developed to identify sites of proteolytic attack. The structure of holoavidin is almost identical to the apoprotein. In particular, the 3-4 loop has the same structure in the apo and holo forms, yet there are marked differences in proteolytic susceptibility of this region. Evidence suggests that the 3-4 loop is rather mobile and flexible in the apoprotein, and that it becomes constrained upon ligand binding. In one crystal structure of the apoprotein, this loop appears constrained by contacts with symmetry-related molecules. Structural analyses suggest that the "lid" to the biotin-binding site, formed by the 3-4 loop, is displaced and made more accessible by HABA binding, thereby enhancing its proteolytic susceptibility. 相似文献
30.